1-102979123-T-G

Position:

• chr1-102979123-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.2611-19A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.689 in 1,611,902 control chromosomes in the GnomAD database, including 392,228 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (29725 hom., cov: 33)
  • Exomes 𝑓: 0.70 (362503 hom.)
• Consequence: COL11A1 NM_001854.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 0.346

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 1-102979123-T-G is Benign according to our data. Variant chr1-102979123-T-G is described in ClinVar as [Benign]. Clinvar id is 258445.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-102979123-T-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL11A1	NM_001854.4	c.2611-19A>C		intron_variant		ENST00000370096.9	NP_001845.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL11A1	ENST00000370096.9	c.2611-19A>C		intron_variant		1	NM_001854.4	ENSP00000359114.3

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89671 AN: 152008 Hom.: 29722 Cov.: 33

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.886

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.913

Gnomad SAS AF: 0.824

Gnomad FIN AF: 0.698

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.620

GnomAD3 exomes AF: 0.696 AC: 174342 AN: 250312 Hom.: 62913 AF XY: 0.709 AC XY: 96011 AN XY: 135400

Gnomad AFR exome AF: 0.245

Gnomad AMR exome AF: 0.693

Gnomad ASJ exome AF: 0.666

Gnomad EAS exome AF: 0.912

Gnomad SAS exome AF: 0.822

Gnomad FIN exome AF: 0.698

Gnomad NFE exome AF: 0.695

Gnomad OTH exome AF: 0.691

GnomAD4 exome AF: 0.699 AC: 1020949 AN: 1459776 Hom.: 362503 Cov.: 38 AF XY: 0.704 AC XY: 511359 AN XY: 726256

Gnomad4 AFR exome AF: 0.243

Gnomad4 AMR exome AF: 0.689

Gnomad4 ASJ exome AF: 0.665

Gnomad4 EAS exome AF: 0.925

Gnomad4 SAS exome AF: 0.819

Gnomad4 FIN exome AF: 0.698

Gnomad4 NFE exome AF: 0.698

Gnomad4 OTH exome AF: 0.684

GnomAD4 genome AF: 0.590 AC: 89687 AN: 152126 Hom.: 29725 Cov.: 33 AF XY: 0.597 AC XY: 44407 AN XY: 74394

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.685

Gnomad4 ASJ AF: 0.683

Gnomad4 EAS AF: 0.913

Gnomad4 SAS AF: 0.824

Gnomad4 FIN AF: 0.698

Gnomad4 NFE AF: 0.701

Gnomad4 OTH AF: 0.622

Alfa AF: 0.617 Hom.: 8245

Bravo AF: 0.572

Asia WGS AF: 0.807 AC: 2807 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

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	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 29, 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. -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

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	-0.81
CADD	Benign	6.9
DANN	Benign	0.51

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: rs11164649; hg19: chr1-103444679; COSMIC: COSV62177130;