rs2622875

Positions:

chr1-103002739-C-T

Variant summary

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

The NM_001854.4(COL11A1):c.2043+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0263 in 1,609,480 control chromosomes in the GnomAD database, including 878 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.044 ( 253 hom., cov: 32)

Exomes 𝑓: 0.024 ( 625 hom. )

Consequence

COL11A1
NM_001854.4 splice_region, intron

Scores

Splicing: ADA: 0.00002870

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -1.19

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=-0.74).

BP6

Variant 1-103002739-C-T is Benign according to our data. Variant chr1-103002739-C-T is described in ClinVar as [Benign]. Clinvar id is 258442.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-103002739-C-T is described in Lovd as [Benign]. Variant chr1-103002739-C-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.095 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.2043+8G>A		splice_region_variant, intron_variant		ENST00000370096.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL11A1	ENST00000370096.9 linkuse as main transcript	c.2043+8G>A		splice_region_variant, intron_variant		1	NM_001854.4	P1	P12107-1

Frequencies

GnomAD3 genomes

AF:

0.0440

AC:

6696

AN:

152022

Hom.:

251

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0972

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0312

Gnomad ASJ

AF:

0.0254

Gnomad EAS

AF:

0.00579

Gnomad SAS

AF:

0.0182

Gnomad FIN

AF:

0.0466

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0202

Gnomad OTH

AF:

0.0461

GnomAD3 exomes

AF:

0.0294

AC:

7378

AN:

251116

Hom.:

178

AF XY:

0.0274

AC XY:

3718

AN XY:

135750

show subpopulations

Gnomad AFR exome

AF:

0.101

Gnomad AMR exome

AF:

0.0349

Gnomad ASJ exome

AF:

0.0299

Gnomad EAS exome

AF:

0.00490

Gnomad SAS exome

AF:

0.0189

Gnomad FIN exome

AF:

0.0432

Gnomad NFE exome

AF:

0.0216

Gnomad OTH exome

AF:

0.0307

GnomAD4 exome

AF:

0.0244

AC:

35570

AN:

1457340

Hom.:

625

Cov.:

AF XY:

0.0238

AC XY:

17263

AN XY:

725366

show subpopulations

Gnomad4 AFR exome

AF:

0.104

Gnomad4 AMR exome

AF:

0.0350

Gnomad4 ASJ exome

AF:

0.0286

Gnomad4 EAS exome

AF:

0.00451

Gnomad4 SAS exome

AF:

0.0188

Gnomad4 FIN exome

AF:

0.0426

Gnomad4 NFE exome

AF:

0.0212

Gnomad4 OTH exome

AF:

0.0316

GnomAD4 genome

AF:

0.0442

AC:

6717

AN:

152140

Hom.:

253

Cov.:

AF XY:

0.0448

AC XY:

3331

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.0975

Gnomad4 AMR

AF:

0.0311

Gnomad4 ASJ

AF:

0.0254

Gnomad4 EAS

AF:

0.00580

Gnomad4 SAS

AF:

0.0185

Gnomad4 FIN

AF:

0.0466

Gnomad4 NFE

AF:

0.0202

Gnomad4 OTH

AF:

0.0451

Alfa

AF:

0.0320

Hom.:

Bravo

AF:

0.0474

Asia WGS

AF:

0.0260

AC:

AN:

3478

EpiCase

AF:

0.0246

EpiControl

AF:

0.0225

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 03, 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. -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 24, 2018	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

Fibrochondrogenesis 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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 12, 2018

Connective tissue disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Apr 01, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.93

DANN

Benign

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000029

dbscSNV1_RF

Benign

0.010

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