NM_001854.4:c.4512T>C

Variant names:

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.4512T>C(p.Gly1504Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.746 in 1,611,910 control chromosomes in the GnomAD database, including 457,887 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 35478 hom., cov: 32)

Exomes 𝑓: 0.76 ( 422409 hom. )

Consequence

COL11A1
NM_001854.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: 0.219

Publications

33 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 (BayesDel_noAF=-0.5).

BP6

Variant 1-102888872-A-G is Benign according to our data. Variant chr1-102888872-A-G is described in ClinVar as Benign. ClinVar VariationId is 258466.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL11A1	NM_001854.4 link	c.4512T>C	p.Gly1504Gly	synonymous_variant	Exon 60 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.4512T>C	p.Gly1504Gly	synonymous_variant	Exon 60 of 67	1	NM_001854.4	ENSP00000359114.3		P12107-1

Frequencies

GnomAD3 genomes

AF:

0.651

AC:

98840

AN:

151896

Hom.:

35469

Cov.:

show subpopulations

Gnomad AFR

AF:

0.315

Gnomad AMI

AF:

0.780

Gnomad AMR

AF:

0.795

Gnomad ASJ

AF:

0.803

Gnomad EAS

AF:

0.742

Gnomad SAS

AF:

0.645

Gnomad FIN

AF:

0.806

Gnomad MID

AF:

0.804

Gnomad NFE

AF:

0.780

Gnomad OTH

AF:

0.712

GnomAD2 exomes

AF:

0.737

AC:

184970

AN:

251086

AF XY:

0.739

show subpopulations

Gnomad AFR exome

AF:

0.304

Gnomad AMR exome

AF:

0.825

Gnomad ASJ exome

AF:

0.794

Gnomad EAS exome

AF:

0.720

Gnomad FIN exome

AF:

0.808

Gnomad NFE exome

AF:

0.777

Gnomad OTH exome

AF:

0.774

GnomAD4 exome

AF:

0.756

AC:

1103516

AN:

1459896

Hom.:

422409

Cov.:

AF XY:

0.755

AC XY:

548116

AN XY:

726384

show subpopulations

African (AFR)

AF:

0.293

AC:

9803

AN:

33434

American (AMR)

AF:

0.822

AC:

36745

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.796

AC:

20798

AN:

26112

East Asian (EAS)

AF:

0.699

AC:

27717

AN:

39678

South Asian (SAS)

AF:

0.653

AC:

56299

AN:

86204

European-Finnish (FIN)

AF:

0.804

AC:

42944

AN:

53412

Middle Eastern (MID)

AF:

0.772

AC:

4447

AN:

5760

European-Non Finnish (NFE)

AF:

0.774

AC:

859883

AN:

1110266

Other (OTH)

AF:

0.744

AC:

44880

AN:

60340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

13949

27898

41847

55796

69745

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20318

40636

60954

81272

101590

<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:

0.650

AC:

98867

AN:

152014

Hom.:

35478

Cov.:

AF XY:

0.655

AC XY:

48665

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.314

AC:

13030

AN:

41436

American (AMR)

AF:

0.795

AC:

12138

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.803

AC:

2787

AN:

3472

East Asian (EAS)

AF:

0.742

AC:

3826

AN:

5156

South Asian (SAS)

AF:

0.645

AC:

3101

AN:

4808

European-Finnish (FIN)

AF:

0.806

AC:

8522

AN:

10572

Middle Eastern (MID)

AF:

0.803

AC:

236

AN:

294

European-Non Finnish (NFE)

AF:

0.780

AC:

53006

AN:

67992

Other (OTH)

AF:

0.715

AC:

1511

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1438

2876

4315

5753

7191

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

772

1544

2316

3088

3860

<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:

0.724

Hom.:

90797

Bravo

AF:

0.639

Asia WGS

AF:

0.683

AC:

2374

AN:

3478

EpiCase

AF:

0.781

EpiControl

AF:

0.785

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

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

Significance:Benign

Review Status:no assertion criteria provided

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

- -

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

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Fibrochondrogenesis 1

Benign:2

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. -

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

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

- -

Stickler syndrome type 2

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

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

- -

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

BayesDel_noAF

Benign

-0.50

CADD

Benign

4.3

(source)

DANN

Benign

0.79

PhyloP100

0.22

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