rs17127203

Positions:

• chr1-102888559-T-C
• chr1-102888559-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.4608+18A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,607,942 control chromosomes in the GnomAD database, including 13,632 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1360 hom., cov: 33)
  • Exomes 𝑓: 0.12 (12272 hom.)
• Consequence: COL11A1 NM_001854.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.0560

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=-0.82).
• BP6: Variant 1-102888559-T-C is Benign according to our data. Variant chr1-102888559-T-C is described in ClinVar as [Benign]. Clinvar id is 258467.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-102888559-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL11A1	NM_001854.4	c.4608+18A>G		intron_variant		ENST00000370096.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL11A1	ENST00000370096.9	c.4608+18A>G		intron_variant		1	NM_001854.4	P1

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19015 AN: 152108 Hom.: 1362 Cov.: 33

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0929

Gnomad ASJ AF: 0.0732

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.0437

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.117

GnomAD3 exomes AF: 0.131 AC: 32699 AN: 250224 Hom.: 2671 AF XY: 0.133 AC XY: 18030 AN XY: 135350

Gnomad AFR exome AF: 0.163

Gnomad AMR exome AF: 0.102

Gnomad ASJ exome AF: 0.0752

Gnomad EAS exome AF: 0.271

Gnomad SAS exome AF: 0.228

Gnomad FIN exome AF: 0.0479

Gnomad NFE exome AF: 0.108

Gnomad OTH exome AF: 0.110

GnomAD4 exome AF: 0.120 AC: 175342 AN: 1455716 Hom.: 12272 Cov.: 29 AF XY: 0.123 AC XY: 88972 AN XY: 724614

Gnomad4 AFR exome AF: 0.166

Gnomad4 AMR exome AF: 0.0999

Gnomad4 ASJ exome AF: 0.0748

Gnomad4 EAS exome AF: 0.295

Gnomad4 SAS exome AF: 0.220

Gnomad4 FIN exome AF: 0.0516

Gnomad4 NFE exome AF: 0.110

Gnomad4 OTH exome AF: 0.120

GnomAD4 genome AF: 0.125 AC: 19016 AN: 152226 Hom.: 1360 Cov.: 33 AF XY: 0.123 AC XY: 9182 AN XY: 74418

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.0929

Gnomad4 ASJ AF: 0.0732

Gnomad4 EAS AF: 0.246

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.0437

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.115

Alfa AF: 0.116 Hom.: 245

Bravo AF: 0.127

Asia WGS AF: 0.230 AC: 800 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

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

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	-0.82
CADD	Benign	5.5
DANN	Benign	0.42

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: rs17127203; hg19: chr1-103354115; COSMIC: COSV62172744; COSMIC: COSV62172744;