1-102886520-C-T

Variant names:

• chr1-102886520-C-T
• rs1463048
• NM_001854.4:c.4858+287G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001854.4(COL11A1):​c.4858+287G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 151,978 control chromosomes in the GnomAD database, including 21,795 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.49 (21795 hom., cov: 32)
• Consequence: COL11A1 NM_001854.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.519
• Publications: 3 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 1-102886520-C-T is Benign according to our data. Variant chr1-102886520-C-T is described in ClinVar as [Benign]. Clinvar id is 681207.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL11A1	NM_001854.4	c.4858+287G>A		intron_variant	Intron 63 of 66	ENST00000370096.9	NP_001845.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL11A1	ENST00000370096.9	c.4858+287G>A		intron_variant	Intron 63 of 66	1	NM_001854.4	ENSP00000359114.3

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74345 AN: 151860 Hom.: 21783 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.657

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.617

Gnomad OTH AF: 0.521

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

GnomAD4 genome AF: 0.489 AC: 74364 AN: 151978 Hom.: 21795 Cov.: 32 AF XY: 0.496 AC XY: 36859 AN XY: 74256

African (AFR) AF: 0.138 AC: 5702 AN: 41458

American (AMR) AF: 0.657 AC: 10031 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 1959 AN: 3472

East Asian (EAS) AF: 0.665 AC: 3438 AN: 5168

South Asian (SAS) AF: 0.570 AC: 2746 AN: 4816

European-Finnish (FIN) AF: 0.638 AC: 6734 AN: 10550

Middle Eastern (MID) AF: 0.569 AC: 165 AN: 290

European-Non Finnish (NFE) AF: 0.617 AC: 41902 AN: 67932

Other (OTH) AF: 0.525 AC: 1109 AN: 2114

Alfa AF: 0.393 Hom.: 1342

Bravo AF: 0.477

Asia WGS AF: 0.589 AC: 2043 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.60
DANN	Benign	0.50
PhyloP100		-0.52
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: rs1463048; hg19: chr1-103352076; COSMIC: COSV62176874; COSMIC: COSV62176874;