Variant 1-102995952-T-A 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.2295+37A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.959 in 1,612,872 control chromosomes in the GnomAD database, including 743,440 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.92 ( 64681 hom., cov: 33)

Exomes 𝑓: 0.96 ( 678759 hom. )

Consequence

COL11A1
NM_001854.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.599

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 1-102995952-T-A is Benign according to our data. Variant chr1-102995952-T-A is described in ClinVar as [Benign]. Clinvar id is 258443.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 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.2295+37A>T		intron_variant		ENST00000370096.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL11A1	ENST00000370096.9 linkuse as main transcript	c.2295+37A>T		intron_variant		1	NM_001854.4	P1	P12107-1

Frequencies

GnomAD3 genomes

AF:

0.919

AC:

139762

AN:

152146

Hom.:

64633

Cov.:

show subpopulations

Gnomad AFR

AF:

0.800

Gnomad AMI

AF:

0.999

Gnomad AMR

AF:

0.953

Gnomad ASJ

AF:

0.904

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.986

Gnomad FIN

AF:

0.969

Gnomad MID

AF:

0.937

Gnomad NFE

AF:

0.964

Gnomad OTH

AF:

0.910

GnomAD3 exomes

AF:

0.956

AC:

240007

AN:

250946

Hom.:

115085

AF XY:

0.961

AC XY:

130390

AN XY:

135724

show subpopulations

Gnomad AFR exome

AF:

0.791

Gnomad AMR exome

AF:

0.972

Gnomad ASJ exome

AF:

0.896

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.986

Gnomad FIN exome

AF:

0.970

Gnomad NFE exome

AF:

0.963

Gnomad OTH exome

AF:

0.951

GnomAD4 exome

AF:

0.964

AC:

1407358

AN:

1460608

Hom.:

678759

Cov.:

AF XY:

0.965

AC XY:

701033

AN XY:

726654

show subpopulations

Gnomad4 AFR exome

AF:

0.787

Gnomad4 AMR exome

AF:

0.969

Gnomad4 ASJ exome

AF:

0.896

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.987

Gnomad4 FIN exome

AF:

0.970

Gnomad4 NFE exome

AF:

0.967

Gnomad4 OTH exome

AF:

0.954

GnomAD4 genome

AF:

0.919

AC:

139868

AN:

152264

Hom.:

64681

Cov.:

AF XY:

0.922

AC XY:

68624

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.800

Gnomad4 AMR

AF:

0.953

Gnomad4 ASJ

AF:

0.904

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.986

Gnomad4 FIN

AF:

0.969

Gnomad4 NFE

AF:

0.964

Gnomad4 OTH

AF:

0.911

Alfa

AF:

0.937

Hom.:

12325

Bravo

AF:

0.912

Asia WGS

AF:

0.983

AC:

3414

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

- -

Fibrochondrogenesis 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

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. -

Stickler syndrome type 2

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

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.39

DANN

Benign

0.52

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