rs2622867

Positions:

• chr1-102995952-T-A
• chr1-102995952-T-C
• chr1-102995952-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.599

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]

ACMG classification

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	Protein	UniProt
COL11A1	NM_001854.4	c.2295+37A>T		intron_variant		ENST00000370096.9	NP_001845.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL11A1	ENST00000370096.9	c.2295+37A>T		intron_variant		1	NM_001854.4	ENSP00000359114	P1

Frequencies

GnomAD3 genomes AF: 0.919 AC: 139762 AN: 152146 Hom.: 64633 Cov.: 33

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

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.: 43 AF XY: 0.965 AC XY: 701033 AN XY: 726654

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.: 33 AF XY: 0.922 AC XY: 68624 AN XY: 74452

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:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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. -

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

- -

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

Other links and lift over

dbSNP: rs2622867; hg19: chr1-103461508;