rs3811161

chr9-134796731-A-G

Variant summary

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

The NM_000093.5(COL5A1):c.2845-117A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 987,228 control chromosomes in the GnomAD database, including 132,268 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.52 (20867 hom., cov: 32)
  • Exomes 𝑓: 0.51 (111401 hom.)
• Consequence: COL5A1 NM_000093.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.78

Genes affected

COL5A1 (HGNC:2209): (collagen type V alpha 1 chain) This gene encodes an alpha chain for one of the low abundance fibrillar collagens. Fibrillar collagen molecules are trimers that can be composed of one or more types of alpha chains. Type V collagen is found in tissues containing type I collagen and appears to regulate the assembly of heterotypic fibers composed of both type I and type V collagen. This gene product is closely related to type XI collagen and it is possible that the collagen chains of types V and XI constitute a single collagen type with tissue-specific chain combinations. The encoded procollagen protein occurs commonly as the heterotrimer pro-alpha1(V)-pro-alpha1(V)-pro-alpha2(V). Mutations in this gene are associated with Ehlers-Danlos syndrome, types I and II. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2013]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 9-134796731-A-G is Benign according to our data. Variant chr9-134796731-A-G is described in ClinVar as [Benign]. Clinvar id is 672276.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL5A1	NM_000093.5	c.2845-117A>G		intron_variant		ENST00000371817.8
COL5A1	NM_001278074.1	c.2845-117A>G		intron_variant
COL5A1	XM_017014266.3	c.2845-117A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL5A1	ENST00000371817.8	c.2845-117A>G		intron_variant		1	NM_000093.5	P4
COL5A1	ENST00000371820.4	c.2845-117A>G		intron_variant		2		A2

Frequencies

GnomAD3 genomes AF: 0.520 AC: 79047 AN: 151924 Hom.: 20852 Cov.: 32

Gnomad AFR AF: 0.571

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.773

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.511

GnomAD4 exome AF: 0.512 AC: 427645 AN: 835186 Hom.: 111401 AF XY: 0.513 AC XY: 225492 AN XY: 439414

Gnomad4 AFR exome AF: 0.573

Gnomad4 AMR exome AF: 0.466

Gnomad4 ASJ exome AF: 0.536

Gnomad4 EAS exome AF: 0.762

Gnomad4 SAS exome AF: 0.545

Gnomad4 FIN exome AF: 0.456

Gnomad4 NFE exome AF: 0.495

Gnomad4 OTH exome AF: 0.522

GnomAD4 genome AF: 0.520 AC: 79113 AN: 152042 Hom.: 20867 Cov.: 32 AF XY: 0.518 AC XY: 38531 AN XY: 74314

Gnomad4 AFR AF: 0.571

Gnomad4 AMR AF: 0.450

Gnomad4 ASJ AF: 0.539

Gnomad4 EAS AF: 0.773

Gnomad4 SAS AF: 0.551

Gnomad4 FIN AF: 0.458

Gnomad4 NFE AF: 0.496

Gnomad4 OTH AF: 0.511

Alfa AF: 0.515 Hom.: 2546

Bravo AF: 0.523

Asia WGS AF: 0.653 AC: 2268 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	-0.97
Cadd	Benign	0.15
Dann	Benign	0.20

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: rs3811161; hg19: chr9-137688577; COSMIC: COSV65667152;