rs17461252

Positions:

• chr1-103017802-T-A

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.1413+18A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0547 in 1,596,772 control chromosomes in the GnomAD database, including 3,049 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.041 (219 hom., cov: 32)
  • Exomes 𝑓: 0.056 (2830 hom.)
• Consequence: COL11A1 NM_001854.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.50

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=-0.9).
• BP6: Variant 1-103017802-T-A is Benign according to our data. Variant chr1-103017802-T-A is described in ClinVar as [Benign]. Clinvar id is 258439.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-103017802-T-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL11A1	NM_001854.4	c.1413+18A>T		intron_variant		ENST00000370096.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL11A1	ENST00000370096.9	c.1413+18A>T		intron_variant		1	NM_001854.4	P1

Frequencies

GnomAD3 genomes AF: 0.0409 AC: 6220 AN: 152082 Hom.: 218 Cov.: 32

Gnomad AFR AF: 0.0109

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0730

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.0207

Gnomad FIN AF: 0.0488

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0577

Gnomad OTH AF: 0.0244

GnomAD3 exomes AF: 0.0547 AC: 13751 AN: 251190 Hom.: 656 AF XY: 0.0507 AC XY: 6882 AN XY: 135760

Gnomad AFR exome AF: 0.0119

Gnomad AMR exome AF: 0.142

Gnomad ASJ exome AF: 0.0102

Gnomad EAS exome AF: 0.00120

Gnomad SAS exome AF: 0.0230

Gnomad FIN exome AF: 0.0534

Gnomad NFE exome AF: 0.0561

Gnomad OTH exome AF: 0.0467

GnomAD4 exome AF: 0.0562 AC: 81198 AN: 1444572 Hom.: 2830 Cov.: 29 AF XY: 0.0550 AC XY: 39600 AN XY: 719804

Gnomad4 AFR exome AF: 0.00880

Gnomad4 AMR exome AF: 0.135

Gnomad4 ASJ exome AF: 0.0107

Gnomad4 EAS exome AF: 0.00227

Gnomad4 SAS exome AF: 0.0239

Gnomad4 FIN exome AF: 0.0570

Gnomad4 NFE exome AF: 0.0605

Gnomad4 OTH exome AF: 0.0503

GnomAD4 genome AF: 0.0409 AC: 6221 AN: 152200 Hom.: 219 Cov.: 32 AF XY: 0.0406 AC XY: 3019 AN XY: 74402

Gnomad4 AFR AF: 0.0108

Gnomad4 AMR AF: 0.0731

Gnomad4 ASJ AF: 0.0101

Gnomad4 EAS AF: 0.00290

Gnomad4 SAS AF: 0.0205

Gnomad4 FIN AF: 0.0488

Gnomad4 NFE AF: 0.0577

Gnomad4 OTH AF: 0.0241

Alfa AF: 0.0464 Hom.: 38

Bravo AF: 0.0423

Asia WGS AF: 0.0140 AC: 49 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

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	GeneDx	Oct 11, 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, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.52
DANN	Benign	0.46

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: rs17461252; hg19: chr1-103483358;