rs3753841

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001854.4(COL11A1):c.3968C>T(p.Pro1323Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.596 in 1,602,454 control chromosomes in the GnomAD database, including 294,801 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1323T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.50 ( 22450 hom., cov: 31)

Exomes 𝑓: 0.61 ( 272351 hom. )

Consequence

COL11A1
NM_001854.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:15

Conservation

PhyloP100: 9.29

Publications

125 publications found

Variant links:

Genes affected

COL11A1 (HGNC:2186): (collagen type XI alpha 1 chain) This gene encodes one of the two alpha chains of type XI collagen, a minor fibrillar collagen. Type XI collagen is a heterotrimer but the third alpha chain is a post-translationally modified alpha 1 type II chain. Mutations in this gene are associated with type II Stickler syndrome and with Marshall syndrome. A single-nucleotide polymorphism in this gene is also associated with susceptibility to lumbar disc herniation. Multiple transcript variants have been identified for this gene. [provided by RefSeq, Nov 2009]

COL11A1 Gene-Disease associations (from GenCC):

Marshall syndrome
Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
Stickler syndrome type 2
Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, PanelApp Australia, Orphanet, Genomics England PanelApp
fibrochondrogenesis 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
hearing loss, autosomal dominant 37
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
autosomal dominant myopia-midfacial retrusion-sensorineural hearing loss-rhizomelic dysplasia syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
fibrochondrogenesis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
autosomal recessive Stickler syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

COL11A1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.535358E-5).

BP6

Variant 1-102914362-G-A is Benign according to our data. Variant chr1-102914362-G-A is described in ClinVar as Benign. ClinVar VariationId is 258461.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL11A1	NM_001854.4 link	c.3968C>T	p.Pro1323Leu	missense_variant	Exon 52 of 67	ENST00000370096.9	NP_001845.3	P12107-1Q59HB5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL11A1	ENST00000370096.9 link	c.3968C>T	p.Pro1323Leu	missense_variant	Exon 52 of 67	1	NM_001854.4	ENSP00000359114.3		P12107-1

Frequencies

GnomAD3 genomes

AF:

0.497

AC:

75315

AN:

151610

Hom.:

22440

Cov.:

show subpopulations

Gnomad AFR

AF:

0.136

Gnomad AMI

AF:

0.628

Gnomad AMR

AF:

0.672

Gnomad ASJ

AF:

0.608

Gnomad EAS

AF:

0.700

Gnomad SAS

AF:

0.589

Gnomad FIN

AF:

0.657

Gnomad MID

AF:

0.589

Gnomad NFE

AF:

0.621

Gnomad OTH

AF:

0.537

GnomAD2 exomes

AF:

0.605

AC:

150972

AN:

249372

AF XY:

0.609

show subpopulations

Gnomad AFR exome

AF:

0.119

Gnomad AMR exome

AF:

0.746

Gnomad ASJ exome

AF:

0.594

Gnomad EAS exome

AF:

0.683

Gnomad FIN exome

AF:

0.667

Gnomad NFE exome

AF:

0.611

Gnomad OTH exome

AF:

0.627

GnomAD4 exome

AF:

0.606

AC:

879585

AN:

1450726

Hom.:

272351

Cov.:

AF XY:

0.608

AC XY:

438568

AN XY:

721758

show subpopulations

African (AFR)

AF:

0.115

AC:

3837

AN:

33396

American (AMR)

AF:

0.738

AC:

32838

AN:

44522

Ashkenazi Jewish (ASJ)

AF:

0.594

AC:

15476

AN:

26038

East Asian (EAS)

AF:

0.674

AC:

26671

AN:

39570

South Asian (SAS)

AF:

0.592

AC:

50200

AN:

84744

European-Finnish (FIN)

AF:

0.665

AC:

35343

AN:

53146

Middle Eastern (MID)

AF:

0.581

AC:

3337

AN:

5748

European-Non Finnish (NFE)

AF:

0.613

AC:

676162

AN:

1103586

Other (OTH)

AF:

0.596

AC:

35721

AN:

59976

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

15105

30210

45314

60419

75524

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18048

36096

54144

72192

90240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.496

AC:

75330

AN:

151728

Hom.:

22450

Cov.:

AF XY:

0.504

AC XY:

37348

AN XY:

74154

show subpopulations

African (AFR)

AF:

0.135

AC:

5599

AN:

41342

American (AMR)

AF:

0.673

AC:

10253

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.608

AC:

2110

AN:

3468

East Asian (EAS)

AF:

0.700

AC:

3609

AN:

5156

South Asian (SAS)

AF:

0.589

AC:

2834

AN:

4812

European-Finnish (FIN)

AF:

0.657

AC:

6894

AN:

10492

Middle Eastern (MID)

AF:

0.595

AC:

175

AN:

294

European-Non Finnish (NFE)

AF:

0.621

AC:

42148

AN:

67914

Other (OTH)

AF:

0.541

AC:

1138

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1555

3109

4664

6218

7773

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

658

1316

1974

2632

3290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.584

Hom.:

129819

Bravo

AF:

0.484

TwinsUK

AF:

0.595

AC:

2206

ALSPAC

AF:

0.618

AC:

2381

ESP6500AA

AF:

0.140

AC:

615

ESP6500EA

AF:

0.612

AC:

5260

ExAC

AF:

0.590

AC:

71557

Asia WGS

AF:

0.605

AC:

2101

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:15

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Sep 29, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Dec 20, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Fibrochondrogenesis 1

Benign:3

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Stickler syndrome type 2

Benign:2

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Hearing loss, autosomal dominant 37

Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Marshall syndrome

Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Uncertain

0.12

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.75

D;.;.;.

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.50

T;T;T;T

MetaRNN

Benign

0.000055

T;T;T;T

MetaSVM

Pathogenic

0.97

MutationAssessor

Uncertain

2.6

M;.;.;.

PhyloP100

9.3

PrimateAI

Uncertain

0.69

PROVEAN

Pathogenic

-5.7

D;D;D;D

REVEL

Uncertain

0.60

Sift

Benign

0.042

D;T;T;T

Sift4G

Benign

0.087

T;T;T;T

Polyphen

0.044

B;P;B;.

Vest4

0.34

MPC

0.12

ClinPred

0.058

GERP RS

5.8

Varity_R

0.32

gMVP

0.32

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over