rs3767272

chr1-103017773-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001854.4(COL11A1):c.1413+47A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.028 in 1,453,522 control chromosomes in the GnomAD database, including 734 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.024 (61 hom., cov: 32)
  • Exomes 𝑓: 0.028 (673 hom.)
• Consequence: COL11A1 NM_001854.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0650

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-103017773-T-C is Benign according to our data. Variant chr1-103017773-T-C is described in ClinVar as [Benign]. Clinvar id is 674969.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL11A1	NM_001854.4	c.1413+47A>G		intron_variant		ENST00000370096.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL11A1	ENST00000370096.9	c.1413+47A>G		intron_variant		1	NM_001854.4	P1

Frequencies

GnomAD3 genomes AF: 0.0241 AC: 3671 AN: 152100 Hom.: 61 Cov.: 32

Gnomad AFR AF: 0.0142

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0274

Gnomad ASJ AF: 0.0421

Gnomad EAS AF: 0.0668

Gnomad SAS AF: 0.0534

Gnomad FIN AF: 0.00273

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0263

Gnomad OTH AF: 0.0291

GnomAD3 exomes AF: 0.0299 AC: 7509 AN: 250830 Hom.: 170 AF XY: 0.0321 AC XY: 4349 AN XY: 135574

Gnomad AFR exome AF: 0.0128

Gnomad AMR exome AF: 0.0159

Gnomad ASJ exome AF: 0.0435

Gnomad EAS exome AF: 0.0750

Gnomad SAS exome AF: 0.0484

Gnomad FIN exome AF: 0.00315

Gnomad NFE exome AF: 0.0284

Gnomad OTH exome AF: 0.0285

GnomAD4 exome AF: 0.0284 AC: 36981 AN: 1301304 Hom.: 673 Cov.: 19 AF XY: 0.0293 AC XY: 19242 AN XY: 656534

Gnomad4 AFR exome AF: 0.0140

Gnomad4 AMR exome AF: 0.0166

Gnomad4 ASJ exome AF: 0.0429

Gnomad4 EAS exome AF: 0.0606

Gnomad4 SAS exome AF: 0.0484

Gnomad4 FIN exome AF: 0.00422

Gnomad4 NFE exome AF: 0.0272

Gnomad4 OTH exome AF: 0.0297

GnomAD4 genome AF: 0.0242 AC: 3683 AN: 152218 Hom.: 61 Cov.: 32 AF XY: 0.0241 AC XY: 1790 AN XY: 74406

Gnomad4 AFR AF: 0.0145

Gnomad4 AMR AF: 0.0274

Gnomad4 ASJ AF: 0.0421

Gnomad4 EAS AF: 0.0669

Gnomad4 SAS AF: 0.0536

Gnomad4 FIN AF: 0.00273

Gnomad4 NFE AF: 0.0263

Gnomad4 OTH AF: 0.0293

Alfa AF: 0.0259 Hom.: 18

Bravo AF: 0.0252

Asia WGS AF: 0.0440 AC: 151 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

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	-0.89
Cadd	Benign	2.6
Dann	Benign	0.32

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: rs3767272; hg19: chr1-103483329; COSMIC: COSV62189404;