Variant rs71664954 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001854.4(COL11A1):c.1944+11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0277 in 1,602,428 control chromosomes in the GnomAD database, including 783 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 62 hom., cov: 32)

Exomes 𝑓: 0.028 ( 721 hom. )

Consequence

COL11A1
NM_001854.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.414

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 (BayesDel_noAF=-0.64).

BP6

Variant 1-103004433-A-G is Benign according to our data. Variant chr1-103004433-A-G is described in ClinVar as [Benign]. Clinvar id is 195479.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-103004433-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0607 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.1944+11T>C		intron_variant		ENST00000370096.9	NP_001845.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL11A1	ENST00000370096.9 linkuse as main transcript	c.1944+11T>C		intron_variant		1	NM_001854.4	ENSP00000359114	P1	P12107-1

Frequencies

GnomAD3 genomes

AF:

0.0241

AC:

3660

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0142

Gnomad AMI

AF:

0.00330

Gnomad AMR

AF:

0.0273

Gnomad ASJ

AF:

0.0424

Gnomad EAS

AF:

0.0664

Gnomad SAS

AF:

0.0534

Gnomad FIN

AF:

0.00273

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0262

Gnomad OTH

AF:

0.0287

GnomAD3 exomes

AF:

0.0299

AC:

7464

AN:

249280

Hom.:

168

AF XY:

0.0321

AC XY:

4334

AN XY:

134894

show subpopulations

Gnomad AFR exome

AF:

0.0128

Gnomad AMR exome

AF:

0.0157

Gnomad ASJ exome

AF:

0.0435

Gnomad EAS exome

AF:

0.0746

Gnomad SAS exome

AF:

0.0493

Gnomad FIN exome

AF:

0.00315

Gnomad NFE exome

AF:

0.0283

Gnomad OTH exome

AF:

0.0283

GnomAD4 exome

AF:

0.0281

AC:

40759

AN:

1450192

Hom.:

721

Cov.:

AF XY:

0.0290

AC XY:

20909

AN XY:

721976

show subpopulations

Gnomad4 AFR exome

AF:

0.0142

Gnomad4 AMR exome

AF:

0.0165

Gnomad4 ASJ exome

AF:

0.0429

Gnomad4 EAS exome

AF:

0.0592

Gnomad4 SAS exome

AF:

0.0490

Gnomad4 FIN exome

AF:

0.00420

Gnomad4 NFE exome

AF:

0.0269

Gnomad4 OTH exome

AF:

0.0296

GnomAD4 genome

AF:

0.0241

AC:

3672

AN:

152236

Hom.:

Cov.:

AF XY:

0.0240

AC XY:

1785

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0145

Gnomad4 AMR

AF:

0.0272

Gnomad4 ASJ

AF:

0.0424

Gnomad4 EAS

AF:

0.0665

Gnomad4 SAS

AF:

0.0536

Gnomad4 FIN

AF:

0.00273

Gnomad4 NFE

AF:

0.0262

Gnomad4 OTH

AF:

0.0289

Alfa

AF:

0.0268

Hom.:

Bravo

AF:

0.0251

Asia WGS

AF:

0.0440

AC:

151

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 05, 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	Eurofins Ntd Llc (ga)	Nov 15, 2014	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
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	-	- -

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	Jan 31, 2024	- -

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

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.85

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