rs11164663

Positions:

chr1-103082941-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001854.4(COL11A1):c.138T>G(p.Asp46Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0758 in 1,612,862 control chromosomes in the GnomAD database, including 5,153 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.083 ( 599 hom., cov: 31)

Exomes 𝑓: 0.075 ( 4554 hom. )

Consequence

COL11A1
NM_001854.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 1.13

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:

COL11A1 (HGNC:):

COL11A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025791824).

BP6

Variant 1-103082941-A-C is Benign according to our data. Variant chr1-103082941-A-C is described in ClinVar as [Benign]. Clinvar id is 258438.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-103082941-A-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL11A1	NM_001854.4 linkuse as main transcript	c.138T>G	p.Asp46Glu	missense_variant	2/67	ENST00000370096.9	NP_001845.3	P12107-1Q59HB5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL11A1	ENST00000370096.9 linkuse as main transcript	c.138T>G	p.Asp46Glu	missense_variant	2/67	1	NM_001854.4	ENSP00000359114.3		P12107-1

Frequencies

GnomAD3 genomes

AF:

0.0833

AC:

12658

AN:

151946

Hom.:

598

Cov.:

show subpopulations

Gnomad AFR

AF:

0.128

Gnomad AMI

AF:

0.0352

Gnomad AMR

AF:

0.0552

Gnomad ASJ

AF:

0.0528

Gnomad EAS

AF:

0.0120

Gnomad SAS

AF:

0.0215

Gnomad FIN

AF:

0.0616

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0781

Gnomad OTH

AF:

0.0783

GnomAD3 exomes

AF:

0.0612

AC:

15343

AN:

250700

Hom.:

581

AF XY:

0.0589

AC XY:

7975

AN XY:

135480

show subpopulations

Gnomad AFR exome

AF:

0.131

Gnomad AMR exome

AF:

0.0341

Gnomad ASJ exome

AF:

0.0539

Gnomad EAS exome

AF:

0.00865

Gnomad SAS exome

AF:

0.0233

Gnomad FIN exome

AF:

0.0609

Gnomad NFE exome

AF:

0.0787

Gnomad OTH exome

AF:

0.0614

GnomAD4 exome

AF:

0.0750

AC:

109519

AN:

1460798

Hom.:

4554

Cov.:

AF XY:

0.0730

AC XY:

53054

AN XY:

726686

show subpopulations

Gnomad4 AFR exome

AF:

0.133

Gnomad4 AMR exome

AF:

0.0354

Gnomad4 ASJ exome

AF:

0.0559

Gnomad4 EAS exome

AF:

0.00885

Gnomad4 SAS exome

AF:

0.0250

Gnomad4 FIN exome

AF:

0.0610

Gnomad4 NFE exome

AF:

0.0825

Gnomad4 OTH exome

AF:

0.0704

GnomAD4 genome

AF:

0.0833

AC:

12672

AN:

152064

Hom.:

599

Cov.:

AF XY:

0.0818

AC XY:

6083

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.128

Gnomad4 AMR

AF:

0.0551

Gnomad4 ASJ

AF:

0.0528

Gnomad4 EAS

AF:

0.0118

Gnomad4 SAS

AF:

0.0218

Gnomad4 FIN

AF:

0.0616

Gnomad4 NFE

AF:

0.0781

Gnomad4 OTH

AF:

0.0789

Alfa

AF:

0.0773

Hom.:

1162

Bravo

AF:

0.0856

TwinsUK

AF:

0.0863

AC:

320

ALSPAC

AF:

0.0851

AC:

328

ESP6500AA

AF:

0.132

AC:

580

ESP6500EA

AF:

0.0820

AC:

705

ExAC

AF:

0.0635

AC:

7703

Asia WGS

AF:

0.0460

AC:

160

AN:

3476

EpiCase

AF:

0.0731

EpiControl

AF:

0.0718

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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. -

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

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.71

DEOGEN2

Benign

0.24

T;.;.;.;.;.;.;.;.

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.23

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.75

T;T;D;T;T;T;T;T;T

MetaRNN

Benign

0.0026

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.41

N;N;N;N;.;.;.;.;.

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.44

N;N;N;N;.;.;.;.;N

REVEL

Benign

0.13

Sift

Benign

0.74

T;T;T;T;.;.;.;.;T

Sift4G

Benign

1.0

T;T;T;T;.;.;.;.;.

Polyphen

0.0

B;B;B;.;.;.;.;.;.

Vest4

0.083

MutPred

0.28

Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);

MPC

0.31

ClinPred

0.019

GERP RS

3.0

Varity_R

0.038

gMVP

0.18

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