rs55821405

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001854.4(COL11A1):c.4416C>A(p.Asp1472Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00334 in 1,613,130 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0029 ( 2 hom., cov: 31)

Exomes 𝑓: 0.0034 ( 19 hom. )

Consequence

COL11A1
NM_001854.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 2.54

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014775157).

BP6

Variant 1-102889503-G-T is Benign according to our data. Variant chr1-102889503-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 198019.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-102889503-G-T is described in Lovd as [Benign]. Variant chr1-102889503-G-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0029 (439/151560) while in subpopulation AMR AF= 0.0037 (56/15154). AF 95% confidence interval is 0.00311. There are 2 homozygotes in gnomad4. There are 204 alleles in male gnomad4 subpopulation. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL11A1	NM_001854.4 linkuse as main transcript	c.4416C>A	p.Asp1472Glu	missense_variant	59/67	ENST00000370096.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL11A1	ENST00000370096.9 linkuse as main transcript	c.4416C>A	p.Asp1472Glu	missense_variant	59/67	1	NM_001854.4	P1	P12107-1

Frequencies

GnomAD3 genomes

AF:

0.00290

AC:

439

AN:

151440

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000534

Gnomad AMI

AF:

0.0286

Gnomad AMR

AF:

0.00370

Gnomad ASJ

AF:

0.0182

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00312

Gnomad FIN

AF:

0.00134

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00348

Gnomad OTH

AF:

0.00289

GnomAD3 exomes

AF:

0.00337

AC:

848

AN:

251434

Hom.:

AF XY:

0.00350

AC XY:

476

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.00240

Gnomad ASJ exome

AF:

0.0185

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00258

Gnomad FIN exome

AF:

0.00152

Gnomad NFE exome

AF:

0.00373

Gnomad OTH exome

AF:

0.00521

GnomAD4 exome

AF:

0.00339

AC:

4951

AN:

1461570

Hom.:

Cov.:

AF XY:

0.00356

AC XY:

2592

AN XY:

727088

show subpopulations

Gnomad4 AFR exome

AF:

0.000628

Gnomad4 AMR exome

AF:

0.00253

Gnomad4 ASJ exome

AF:

0.0180

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00323

Gnomad4 FIN exome

AF:

0.00163

Gnomad4 NFE exome

AF:

0.00334

Gnomad4 OTH exome

AF:

0.00407

GnomAD4 genome

AF:

0.00290

AC:

439

AN:

151560

Hom.:

Cov.:

AF XY:

0.00275

AC XY:

204

AN XY:

74062

show subpopulations

Gnomad4 AFR

AF:

0.000532

Gnomad4 AMR

AF:

0.00370

Gnomad4 ASJ

AF:

0.0182

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00313

Gnomad4 FIN

AF:

0.00134

Gnomad4 NFE

AF:

0.00348

Gnomad4 OTH

AF:

0.00286

Alfa

AF:

0.00406

Hom.:

Bravo

AF:

0.00306

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00407

AC:

ExAC

AF:

0.00294

AC:

357

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.00420

EpiControl

AF:

0.00450

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 25, 2018	This variant is associated with the following publications: (PMID: 15922184, 27353947, 24036952) -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2024	COL11A1: PP3, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 30, 2024	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Oct 03, 2014

- -

COL11A1-related condition

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 01, 2021

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Fibrochondrogenesis 1

Benign:1

Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Stickler syndrome type 2

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Connective tissue disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Human Genetics, Inc, Center for Human Genetics, Inc

Nov 01, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.64

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Uncertain

-0.010

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Uncertain

0.79

D;.;.;.

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.62

T;T;T;T

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.015

T;T;T;T

MetaSVM

Uncertain

0.34

MutationAssessor

Benign

-0.75

N;.;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-3.5

D;D;D;D

REVEL

Uncertain

0.55

Sift

Benign

0.15

T;T;T;T

Sift4G

Benign

0.24

T;T;T;T

Polyphen

1.0

D;D;D;.

Vest4

0.69

MutPred

0.28

Loss of methylation at R1473 (P = 0.1799);.;.;.;

MVP

0.91

MPC

0.11

ClinPred

0.023

GERP RS

4.5

Varity_R

0.32

gMVP

0.14

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