rs2786125

Variant names:

• chr1-102996917-A-G
• rs2786125
• NM_001854.4:c.2241+163T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-102996917-A-G
• chr1-102996917-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001854.4(COL11A1):​c.2241+163T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.862 in 151,854 control chromosomes in the GnomAD database, including 57,469 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.86 (57469 hom., cov: 32)
• Consequence: COL11A1 NM_001854.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.22
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• Marshall syndrome

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
• Stickler syndrome type 2

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, PanelApp Australia, Orphanet, Genomics England PanelApp
• fibrochondrogenesis 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• hearing loss, autosomal dominant 37

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• autosomal dominant myopia-midfacial retrusion-sensorineural hearing loss-rhizomelic dysplasia syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• fibrochondrogenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal recessive Stickler syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 1-102996917-A-G is Benign according to our data. Variant chr1-102996917-A-G is described in ClinVar as Benign. ClinVar VariationId is 1257210.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.931 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL11A1	NM_001854.4	c.2241+163T>C		intron_variant	Intron 26 of 66	ENST00000370096.9	NP_001845.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL11A1	ENST00000370096.9	c.2241+163T>C		intron_variant	Intron 26 of 66	1	NM_001854.4	ENSP00000359114.3

Frequencies

GnomAD3 genomes AF: 0.862 AC: 130793 AN: 151734 Hom.: 57435 Cov.: 32

Gnomad AFR AF: 0.672

Gnomad AMI AF: 0.996

Gnomad AMR AF: 0.914

Gnomad ASJ AF: 0.862

Gnomad EAS AF: 0.934

Gnomad SAS AF: 0.931

Gnomad FIN AF: 0.966

Gnomad MID AF: 0.843

Gnomad NFE AF: 0.937

Gnomad OTH AF: 0.863

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.862 AC: 130879 AN: 151854 Hom.: 57469 Cov.: 32 AF XY: 0.866 AC XY: 64275 AN XY: 74226

African (AFR) AF: 0.672 AC: 27860 AN: 41428

American (AMR) AF: 0.914 AC: 13902 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.862 AC: 2982 AN: 3460

East Asian (EAS) AF: 0.934 AC: 4834 AN: 5174

South Asian (SAS) AF: 0.932 AC: 4498 AN: 4828

European-Finnish (FIN) AF: 0.966 AC: 10233 AN: 10588

Middle Eastern (MID) AF: 0.849 AC: 248 AN: 292

European-Non Finnish (NFE) AF: 0.937 AC: 63590 AN: 67850

Other (OTH) AF: 0.864 AC: 1824 AN: 2112

Alfa AF: 0.900 Hom.: 89689

Bravo AF: 0.850

Asia WGS AF: 0.931 AC: 3218 AN: 3458

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.3
DANN	Benign	0.75
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2786125; hg19: chr1-103462473;