9-134796811-A-G

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.2845-37A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 1,600,080 control chromosomes in the GnomAD database, including 177,193 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.49 (18434 hom., cov: 33)
  • Exomes 𝑓: 0.46 (158759 hom.)
• Consequence: COL5A1 NM_000093.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.300

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=-0.98).
• BP6: Variant 9-134796811-A-G is Benign according to our data. Variant chr9-134796811-A-G is described in ClinVar as [Benign]. Clinvar id is 255072.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL5A1	NM_000093.5	c.2845-37A>G		intron_variant		ENST00000371817.8
COL5A1	NM_001278074.1	c.2845-37A>G		intron_variant
COL5A1	XM_017014266.3	c.2845-37A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL5A1	ENST00000371817.8	c.2845-37A>G		intron_variant		1	NM_000093.5	P4
COL5A1	ENST00000371820.4	c.2845-37A>G		intron_variant		2		A2

Frequencies

GnomAD3 genomes AF: 0.487 AC: 74000 AN: 151858 Hom.: 18424 Cov.: 33

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.742

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.474

GnomAD3 exomes AF: 0.482 AC: 120722 AN: 250660 Hom.: 30177 AF XY: 0.477 AC XY: 64696 AN XY: 135614

Gnomad AFR exome AF: 0.558

Gnomad AMR exome AF: 0.449

Gnomad ASJ exome AF: 0.498

Gnomad EAS exome AF: 0.754

Gnomad SAS exome AF: 0.467

Gnomad FIN exome AF: 0.417

Gnomad NFE exome AF: 0.452

Gnomad OTH exome AF: 0.463

GnomAD4 exome AF: 0.465 AC: 672713 AN: 1448104 Hom.: 158759 Cov.: 31 AF XY: 0.465 AC XY: 335299 AN XY: 721446

Gnomad4 AFR exome AF: 0.551

Gnomad4 AMR exome AF: 0.446

Gnomad4 ASJ exome AF: 0.492

Gnomad4 EAS exome AF: 0.715

Gnomad4 SAS exome AF: 0.467

Gnomad4 FIN exome AF: 0.417

Gnomad4 NFE exome AF: 0.454

Gnomad4 OTH exome AF: 0.477

GnomAD4 genome AF: 0.487 AC: 74055 AN: 151976 Hom.: 18434 Cov.: 33 AF XY: 0.485 AC XY: 35999 AN XY: 74276

Gnomad4 AFR AF: 0.554

Gnomad4 AMR AF: 0.423

Gnomad4 ASJ AF: 0.499

Gnomad4 EAS AF: 0.741

Gnomad4 SAS AF: 0.464

Gnomad4 FIN AF: 0.417

Gnomad4 NFE AF: 0.458

Gnomad4 OTH AF: 0.472

Alfa AF: 0.458 Hom.: 26797

Bravo AF: 0.492

Asia WGS AF: 0.580 AC: 2014 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

Jul 30, 2021

- -

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. -

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

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	1.9
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: rs3811159; hg19: chr9-137688657; COSMIC: COSV65665298;