9-134795060-C-T

Position:

• chr9-134795060-C-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.2701-22C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 1,609,636 control chromosomes in the GnomAD database, including 281,966 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.65 (33155 hom., cov: 32)
  • Exomes 𝑓: 0.58 (248811 hom.)
• Consequence: COL5A1 NM_000093.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.278

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=-0.66).
• BP6: Variant 9-134795060-C-T is Benign according to our data. Variant chr9-134795060-C-T is described in ClinVar as [Benign]. Clinvar id is 255069.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL5A1	NM_000093.5	c.2701-22C>T		intron_variant		ENST00000371817.8	NP_000084.3
COL5A1	NM_001278074.1	c.2701-22C>T		intron_variant			NP_001265003.1
COL5A1	XM_017014266.3	c.2701-22C>T		intron_variant			XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8	c.2701-22C>T		intron_variant		1	NM_000093.5	ENSP00000360882.3
COL5A1	ENST00000371820.4	c.2701-22C>T		intron_variant		2		ENSP00000360885.4

Frequencies

GnomAD3 genomes AF: 0.649 AC: 98523 AN: 151908 Hom.: 33113 Cov.: 32

Gnomad AFR AF: 0.832

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.822

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.631

GnomAD3 exomes AF: 0.604 AC: 151063 AN: 250244 Hom.: 47019 AF XY: 0.597 AC XY: 80848 AN XY: 135524

Gnomad AFR exome AF: 0.844

Gnomad AMR exome AF: 0.532

Gnomad ASJ exome AF: 0.611

Gnomad EAS exome AF: 0.834

Gnomad SAS exome AF: 0.569

Gnomad FIN exome AF: 0.552

Gnomad NFE exome AF: 0.574

Gnomad OTH exome AF: 0.579

GnomAD4 exome AF: 0.580 AC: 845558 AN: 1457608 Hom.: 248811 Cov.: 39 AF XY: 0.580 AC XY: 420389 AN XY: 725372

Gnomad4 AFR exome AF: 0.848

Gnomad4 AMR exome AF: 0.534

Gnomad4 ASJ exome AF: 0.609

Gnomad4 EAS exome AF: 0.800

Gnomad4 SAS exome AF: 0.568

Gnomad4 FIN exome AF: 0.548

Gnomad4 NFE exome AF: 0.566

Gnomad4 OTH exome AF: 0.604

GnomAD4 genome AF: 0.649 AC: 98624 AN: 152028 Hom.: 33155 Cov.: 32 AF XY: 0.645 AC XY: 47896 AN XY: 74292

Gnomad4 AFR AF: 0.832

Gnomad4 AMR AF: 0.542

Gnomad4 ASJ AF: 0.610

Gnomad4 EAS AF: 0.822

Gnomad4 SAS AF: 0.574

Gnomad4 FIN AF: 0.553

Gnomad4 NFE AF: 0.574

Gnomad4 OTH AF: 0.630

Alfa AF: 0.626 Hom.: 7944

Bravo AF: 0.659

Asia WGS AF: 0.720 AC: 2503 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

- -

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	-0.66
CADD	Benign	14
DANN	Benign	0.92

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: rs4072883; hg19: chr9-137686906; COSMIC: COSV65667137;