rs71664966

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001854.4(COL11A1):c.660T>C(p.Ile220Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0668 in 1,560,958 control chromosomes in the GnomAD database, including 3,699 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 534 hom., cov: 30)

Exomes 𝑓: 0.064 ( 3165 hom. )

Consequence

COL11A1
NM_001854.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 1.05

Publications

13 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 1-103031236-A-G is Benign according to our data. Variant chr1-103031236-A-G is described in ClinVar as Benign. ClinVar VariationId is 93969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.05 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL11A1	NM_001854.4 link	c.660T>C	p.Ile220Ile	synonymous_variant	Exon 5 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.660T>C	p.Ile220Ile	synonymous_variant	Exon 5 of 67	1	NM_001854.4	ENSP00000359114.3		P12107-1

Frequencies

GnomAD3 genomes

AF:

0.111

AC:

11906

AN:

107652

Hom.:

531

Cov.:

show subpopulations

Gnomad AFR

AF:

0.144

Gnomad AMI

AF:

0.00629

Gnomad AMR

AF:

0.116

Gnomad ASJ

AF:

0.0949

Gnomad EAS

AF:

0.111

Gnomad SAS

AF:

0.142

Gnomad FIN

AF:

0.156

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.0812

Gnomad OTH

AF:

0.124

GnomAD2 exomes

AF:

0.0706

AC:

16976

AN:

240598

AF XY:

0.0702

show subpopulations

Gnomad AFR exome

AF:

0.121

Gnomad AMR exome

AF:

0.0543

Gnomad ASJ exome

AF:

0.0814

Gnomad EAS exome

AF:

0.0801

Gnomad FIN exome

AF:

0.107

Gnomad NFE exome

AF:

0.0613

Gnomad OTH exome

AF:

0.0718

GnomAD4 exome

AF:

0.0635

AC:

92314

AN:

1453192

Hom.:

3165

Cov.:

AF XY:

0.0635

AC XY:

45903

AN XY:

723168

show subpopulations

African (AFR)

AF:

0.127

AC:

4234

AN:

33340

American (AMR)

AF:

0.0551

AC:

2457

AN:

44556

Ashkenazi Jewish (ASJ)

AF:

0.0791

AC:

2064

AN:

26090

East Asian (EAS)

AF:

0.0639

AC:

2529

AN:

39578

South Asian (SAS)

AF:

0.0674

AC:

5807

AN:

86130

European-Finnish (FIN)

AF:

0.0944

AC:

4433

AN:

46940

Middle Eastern (MID)

AF:

0.0947

AC:

544

AN:

5746

European-Non Finnish (NFE)

AF:

0.0594

AC:

65968

AN:

1110578

Other (OTH)

AF:

0.0710

AC:

4278

AN:

60234

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.437

Heterozygous variant carriers

4478

8955

13433

17910

22388

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2568

5136

7704

10272

12840

<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:

0.111

AC:

11931

AN:

107766

Hom.:

534

Cov.:

AF XY:

0.114

AC XY:

5882

AN XY:

51596

show subpopulations

African (AFR)

AF:

0.144

AC:

4815

AN:

33386

American (AMR)

AF:

0.115

AC:

1001

AN:

8684

Ashkenazi Jewish (ASJ)

AF:

0.0949

AC:

253

AN:

2666

East Asian (EAS)

AF:

0.111

AC:

368

AN:

3330

South Asian (SAS)

AF:

0.143

AC:

342

AN:

2398

European-Finnish (FIN)

AF:

0.156

AC:

966

AN:

6210

Middle Eastern (MID)

AF:

0.201

AC:

AN:

224

European-Non Finnish (NFE)

AF:

0.0812

AC:

3973

AN:

48904

Other (OTH)

AF:

0.123

AC:

164

AN:

1328

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

474

948

1423

1897

2371

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

252

378

504

630

<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:

0.0682

Hom.:

123

Bravo

AF:

0.0812

Asia WGS

AF:

0.0700

AC:

241

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Oct 04, 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. -

Sep 26, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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

- -

Fibrochondrogenesis 1

Benign:1

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. -

Stickler syndrome type 2

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

8.7

(source)

DANN

Benign

0.80

PhyloP100

1.0

Mutation Taster

=93/7

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