rs73558067

chr9-134753816-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.1720-34C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 1,565,750 control chromosomes in the GnomAD database, including 41,227 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3527 hom., cov: 28)
  • Exomes 𝑓: 0.22 (37700 hom.)
• Consequence: COL5A1 NM_000093.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.14

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=-0.91).
• BP6: Variant 9-134753816-C-T is Benign according to our data. Variant chr9-134753816-C-T is described in ClinVar as [Benign]. Clinvar id is 255054.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL5A1	NM_000093.5	c.1720-34C>T		intron_variant		ENST00000371817.8
COL5A1	NM_001278074.1	c.1720-34C>T		intron_variant
COL5A1	XM_017014266.3	c.1720-34C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL5A1	ENST00000371817.8	c.1720-34C>T		intron_variant		1	NM_000093.5	P4
COL5A1	ENST00000371820.4	c.1720-34C>T		intron_variant		2		A2

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31456 AN: 150336 Hom.: 3526 Cov.: 28

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.207

GnomAD3 exomes AF: 0.210 AC: 52572 AN: 249872 Hom.: 6097 AF XY: 0.212 AC XY: 28632 AN XY: 135366

Gnomad AFR exome AF: 0.183

Gnomad AMR exome AF: 0.119

Gnomad ASJ exome AF: 0.138

Gnomad EAS exome AF: 0.384

Gnomad SAS exome AF: 0.179

Gnomad FIN exome AF: 0.219

Gnomad NFE exome AF: 0.228

Gnomad OTH exome AF: 0.197

GnomAD4 exome AF: 0.224 AC: 317155 AN: 1415296 Hom.: 37700 Cov.: 27 AF XY: 0.223 AC XY: 157338 AN XY: 706322

Gnomad4 AFR exome AF: 0.179

Gnomad4 AMR exome AF: 0.126

Gnomad4 ASJ exome AF: 0.138

Gnomad4 EAS exome AF: 0.377

Gnomad4 SAS exome AF: 0.181

Gnomad4 FIN exome AF: 0.221

Gnomad4 NFE exome AF: 0.230

Gnomad4 OTH exome AF: 0.218

GnomAD4 genome AF: 0.209 AC: 31447 AN: 150454 Hom.: 3527 Cov.: 28 AF XY: 0.207 AC XY: 15215 AN XY: 73390

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.361

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.218

Gnomad4 NFE AF: 0.230

Gnomad4 OTH AF: 0.204

Alfa AF: 0.213 Hom.: 686

Bravo AF: 0.209

Asia WGS AF: 0.216 AC: 750 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 18, 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	-0.91
Cadd	Benign	0.29
Dann	Benign	0.56

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: rs73558067; hg19: chr9-137645662; COSMIC: COSV65670629;