rs3753841

Positions:

Variant summary

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

The NM_001854.4(COL11A1):c.3968C>T(p.Pro1323Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.596 in 1,602,454 control chromosomes in the GnomAD database, including 294,801 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1323T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.50 ( 22450 hom., cov: 31)

Exomes 𝑓: 0.61 ( 272351 hom. )

Consequence

COL11A1
NM_001854.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:15

Conservation

PhyloP100: 9.29

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=5.535358E-5).

BP6

Variant 1-102914362-G-A is Benign according to our data. Variant chr1-102914362-G-A is described in ClinVar as [Benign]. Clinvar id is 258461.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-102914362-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.681 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.3968C>T	p.Pro1323Leu	missense_variant	52/67	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.3968C>T	p.Pro1323Leu	missense_variant	52/67	1	NM_001854.4	ENSP00000359114.3		P12107-1

Frequencies

GnomAD3 genomes

AF:

0.497

AC:

75315

AN:

151610

Hom.:

22440

Cov.:

show subpopulations

Gnomad AFR

AF:

0.136

Gnomad AMI

AF:

0.628

Gnomad AMR

AF:

0.672

Gnomad ASJ

AF:

0.608

Gnomad EAS

AF:

0.700

Gnomad SAS

AF:

0.589

Gnomad FIN

AF:

0.657

Gnomad MID

AF:

0.589

Gnomad NFE

AF:

0.621

Gnomad OTH

AF:

0.537

GnomAD3 exomes

AF:

0.605

AC:

150972

AN:

249372

Hom.:

48337

AF XY:

0.609

AC XY:

82080

AN XY:

134824

show subpopulations

Gnomad AFR exome

AF:

0.119

Gnomad AMR exome

AF:

0.746

Gnomad ASJ exome

AF:

0.594

Gnomad EAS exome

AF:

0.683

Gnomad SAS exome

AF:

0.590

Gnomad FIN exome

AF:

0.667

Gnomad NFE exome

AF:

0.611

Gnomad OTH exome

AF:

0.627

GnomAD4 exome

AF:

0.606

AC:

879585

AN:

1450726

Hom.:

272351

Cov.:

AF XY:

0.608

AC XY:

438568

AN XY:

721758

show subpopulations

Gnomad4 AFR exome

AF:

0.115

Gnomad4 AMR exome

AF:

0.738

Gnomad4 ASJ exome

AF:

0.594

Gnomad4 EAS exome

AF:

0.674

Gnomad4 SAS exome

AF:

0.592

Gnomad4 FIN exome

AF:

0.665

Gnomad4 NFE exome

AF:

0.613

Gnomad4 OTH exome

AF:

0.596

GnomAD4 genome

AF:

0.496

AC:

75330

AN:

151728

Hom.:

22450

Cov.:

AF XY:

0.504

AC XY:

37348

AN XY:

74154

show subpopulations

Gnomad4 AFR

AF:

0.135

Gnomad4 AMR

AF:

0.673

Gnomad4 ASJ

AF:

0.608

Gnomad4 EAS

AF:

0.700

Gnomad4 SAS

AF:

0.589

Gnomad4 FIN

AF:

0.657

Gnomad4 NFE

AF:

0.621

Gnomad4 OTH

AF:

0.541

Alfa

AF:

0.597

Hom.:

70259

Bravo

AF:

0.484

TwinsUK

AF:

0.595

AC:

2206

ALSPAC

AF:

0.618

AC:

2381

ESP6500AA

AF:

0.140

AC:

615

ESP6500EA

AF:

0.612

AC:

5260

ExAC

AF:

0.590

AC:

71557

Asia WGS

AF:

0.605

AC:

2101

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:15

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Dec 20, 2016	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 29, 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, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
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	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Fibrochondrogenesis 1

Benign:3

Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 22, 2021	- -
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:2

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

Stickler syndrome type 2

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 22, 2021	- -
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. -

Hearing loss, autosomal dominant 37

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Marshall syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Uncertain

0.12

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.75

D;.;.;.

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.50

T;T;T;T

MetaRNN

Benign

0.000055

T;T;T;T

MetaSVM

Pathogenic

0.97

MutationAssessor

Uncertain

2.6

M;.;.;.

PrimateAI

Uncertain

0.69

PROVEAN

Pathogenic

-5.7

D;D;D;D

REVEL

Uncertain

0.60

Sift

Benign

0.042

D;T;T;T

Sift4G

Benign

0.087

T;T;T;T

Polyphen

0.044

B;P;B;.

Vest4

0.34

MPC

0.12

ClinPred

0.058

GERP RS

5.8

Varity_R

0.32

gMVP

0.32

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