rs17127203

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.4608+18A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,607,942 control chromosomes in the GnomAD database, including 13,632 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1360 hom., cov: 33)

Exomes 𝑓: 0.12 ( 12272 hom. )

Consequence

COL11A1
NM_001854.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.0560

Publications

10 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=-0.82).

BP6

Variant 1-102888559-T-C is Benign according to our data. Variant chr1-102888559-T-C is described in ClinVar as Benign. ClinVar VariationId is 258467.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL11A1	NM_001854.4 link	c.4608+18A>G		intron_variant	Intron 62 of 66	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.4608+18A>G		intron_variant	Intron 62 of 66	1	NM_001854.4	ENSP00000359114.3		P12107-1

Frequencies

GnomAD3 genomes

AF:

0.125

AC:

19015

AN:

152108

Hom.:

1362

Cov.:

show subpopulations

Gnomad AFR

AF:

0.163

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.0929

Gnomad ASJ

AF:

0.0732

Gnomad EAS

AF:

0.247

Gnomad SAS

AF:

0.242

Gnomad FIN

AF:

0.0437

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.108

Gnomad OTH

AF:

0.117

GnomAD2 exomes

AF:

0.131

AC:

32699

AN:

250224

AF XY:

0.133

show subpopulations

Gnomad AFR exome

AF:

0.163

Gnomad AMR exome

AF:

0.102

Gnomad ASJ exome

AF:

0.0752

Gnomad EAS exome

AF:

0.271

Gnomad FIN exome

AF:

0.0479

Gnomad NFE exome

AF:

0.108

Gnomad OTH exome

AF:

0.110

GnomAD4 exome

AF:

0.120

AC:

175342

AN:

1455716

Hom.:

12272

Cov.:

AF XY:

0.123

AC XY:

88972

AN XY:

724614

show subpopulations

African (AFR)

AF:

0.166

AC:

5536

AN:

33364

American (AMR)

AF:

0.0999

AC:

4459

AN:

44622

Ashkenazi Jewish (ASJ)

AF:

0.0748

AC:

1951

AN:

26090

East Asian (EAS)

AF:

0.295

AC:

11679

AN:

39622

South Asian (SAS)

AF:

0.220

AC:

18959

AN:

86118

European-Finnish (FIN)

AF:

0.0516

AC:

2755

AN:

53366

Middle Eastern (MID)

AF:

0.112

AC:

644

AN:

5756

European-Non Finnish (NFE)

AF:

0.110

AC:

122140

AN:

1106622

Other (OTH)

AF:

0.120

AC:

7219

AN:

60156

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

8457

16914

25372

33829

42286

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4692

9384

14076

18768

23460

<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:

0.125

AC:

19016

AN:

152226

Hom.:

1360

Cov.:

AF XY:

0.123

AC XY:

9182

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.163

AC:

6777

AN:

41542

American (AMR)

AF:

0.0929

AC:

1419

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.0732

AC:

254

AN:

3470

East Asian (EAS)

AF:

0.246

AC:

1274

AN:

5172

South Asian (SAS)

AF:

0.241

AC:

1164

AN:

4826

European-Finnish (FIN)

AF:

0.0437

AC:

464

AN:

10614

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.108

AC:

7362

AN:

68004

Other (OTH)

AF:

0.115

AC:

244

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

840

1680

2521

3361

4201

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

224

448

672

896

1120

<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:

0.113

Hom.:

391

Bravo

AF:

0.127

Asia WGS

AF:

0.230

AC:

800

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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

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

- -

Oct 03, 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. -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.5

(source)

DANN

Benign

0.42

PhyloP100

-0.056

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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