rs1012281

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001854.4(COL11A1):c.3168+15A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0666 in 1,606,974 control chromosomes in the GnomAD database, including 4,029 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.056 ( 269 hom., cov: 32)

Exomes 𝑓: 0.068 ( 3760 hom. )

Consequence

COL11A1
NM_001854.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.25

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 1-102961851-T-C is Benign according to our data. Variant chr1-102961851-T-C is described in ClinVar as [Benign]. Clinvar id is 258455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-102961851-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL11A1	NM_001854.4 linkuse as main transcript	c.3168+15A>G		intron_variant		ENST00000370096.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL11A1	ENST00000370096.9 linkuse as main transcript	c.3168+15A>G		intron_variant		1	NM_001854.4	P1	P12107-1

Frequencies

GnomAD3 genomes

AF:

0.0558

AC:

8485

AN:

152114

Hom.:

269

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0405

Gnomad AMI

AF:

0.0362

Gnomad AMR

AF:

0.0438

Gnomad ASJ

AF:

0.0395

Gnomad EAS

AF:

0.0116

Gnomad SAS

AF:

0.0221

Gnomad FIN

AF:

0.0599

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0741

Gnomad OTH

AF:

0.0566

GnomAD3 exomes

AF:

0.0518

AC:

12898

AN:

249076

Hom.:

416

AF XY:

0.0516

AC XY:

6938

AN XY:

134460

show subpopulations

Gnomad AFR exome

AF:

0.0380

Gnomad AMR exome

AF:

0.0281

Gnomad ASJ exome

AF:

0.0422

Gnomad EAS exome

AF:

0.00868

Gnomad SAS exome

AF:

0.0236

Gnomad FIN exome

AF:

0.0596

Gnomad NFE exome

AF:

0.0747

Gnomad OTH exome

AF:

0.0563

GnomAD4 exome

AF:

0.0678

AC:

98559

AN:

1454742

Hom.:

3760

Cov.:

AF XY:

0.0665

AC XY:

48152

AN XY:

724020

show subpopulations

Gnomad4 AFR exome

AF:

0.0349

Gnomad4 AMR exome

AF:

0.0294

Gnomad4 ASJ exome

AF:

0.0452

Gnomad4 EAS exome

AF:

0.00900

Gnomad4 SAS exome

AF:

0.0253

Gnomad4 FIN exome

AF:

0.0596

Gnomad4 NFE exome

AF:

0.0771

Gnomad4 OTH exome

AF:

0.0599

GnomAD4 genome

AF:

0.0558

AC:

8493

AN:

152232

Hom.:

269

Cov.:

AF XY:

0.0547

AC XY:

4074

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0404

Gnomad4 AMR

AF:

0.0438

Gnomad4 ASJ

AF:

0.0395

Gnomad4 EAS

AF:

0.0114

Gnomad4 SAS

AF:

0.0226

Gnomad4 FIN

AF:

0.0599

Gnomad4 NFE

AF:

0.0741

Gnomad4 OTH

AF:

0.0575

Alfa

AF:

0.0655

Hom.:

156

Bravo

AF:

0.0542

Asia WGS

AF:

0.0430

AC:

149

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 06, 2016	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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -

Fibrochondrogenesis 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Stickler syndrome type 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

Cadd

Benign

Dann

Benign

0.74

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over