rs3811152

Positions:

• chr9-134810213-G-C
• chr9-134810213-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000093.5(COL5A1):​c.3475-42G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 1,607,744 control chromosomes in the GnomAD database, including 19,120 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (5975 hom., cov: 34)
  • Exomes 𝑓: 0.12 (13145 hom.)
• Consequence: COL5A1 NM_000093.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.00800

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 9-134810213-G-C is Benign according to our data. Variant chr9-134810213-G-C is described in ClinVar as [Benign]. Clinvar id is 255078.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL5A1	NM_000093.5	c.3475-42G>C		intron_variant		ENST00000371817.8
COL5A1	NM_001278074.1	c.3475-42G>C		intron_variant
COL5A1	XM_017014266.3	c.3475-42G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL5A1	ENST00000371817.8	c.3475-42G>C		intron_variant		1	NM_000093.5	P4
COL5A1	ENST00000371820.4	c.3475-42G>C		intron_variant		2		A2
COL5A1	ENST00000463925.1	n.331-42G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32967 AN: 152124 Hom.: 5950 Cov.: 34

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.0887

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.195

GnomAD3 exomes AF: 0.135 AC: 33843 AN: 250972 Hom.: 3641 AF XY: 0.129 AC XY: 17455 AN XY: 135758

Gnomad AFR exome AF: 0.510

Gnomad AMR exome AF: 0.0978

Gnomad ASJ exome AF: 0.125

Gnomad EAS exome AF: 0.122

Gnomad SAS exome AF: 0.128

Gnomad FIN exome AF: 0.0923

Gnomad NFE exome AF: 0.106

Gnomad OTH exome AF: 0.126

GnomAD4 exome AF: 0.118 AC: 171973 AN: 1455502 Hom.: 13145 Cov.: 30 AF XY: 0.117 AC XY: 84910 AN XY: 724490

Gnomad4 AFR exome AF: 0.514

Gnomad4 AMR exome AF: 0.105

Gnomad4 ASJ exome AF: 0.130

Gnomad4 EAS exome AF: 0.115

Gnomad4 SAS exome AF: 0.125

Gnomad4 FIN exome AF: 0.0906

Gnomad4 NFE exome AF: 0.106

Gnomad4 OTH exome AF: 0.140

GnomAD4 genome AF: 0.217 AC: 33039 AN: 152242 Hom.: 5975 Cov.: 34 AF XY: 0.211 AC XY: 15729 AN XY: 74430

Gnomad4 AFR AF: 0.500

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.0887

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.198

Alfa AF: 0.0925 Hom.: 241

Bravo AF: 0.232

Asia WGS AF: 0.181 AC: 630 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Fibromuscular dysplasia, multifocal Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Mar 15, 2022

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Ehlers-Danlos syndrome, classic type, 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Mar 15, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.1
DANN	Benign	0.37

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: rs3811152; hg19: chr9-137702059; COSMIC: COSV65667215;