rs13301426

Positions:

• chr9-134786075-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.2646+27C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0717 in 1,593,512 control chromosomes in the GnomAD database, including 4,269 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.073 (430 hom., cov: 33)
  • Exomes 𝑓: 0.072 (3839 hom.)
• Consequence: COL5A1 NM_000093.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.11

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 9-134786075-C-T is Benign according to our data. Variant chr9-134786075-C-T is described in ClinVar as [Benign]. Clinvar id is 255067.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL5A1	NM_000093.5	c.2646+27C>T		intron_variant		ENST00000371817.8	NP_000084.3
COL5A1	NM_001278074.1	c.2646+27C>T		intron_variant			NP_001265003.1
COL5A1	XM_017014266.3	c.2646+27C>T		intron_variant			XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8	c.2646+27C>T		intron_variant		1	NM_000093.5	ENSP00000360882	P4
COL5A1	ENST00000371820.4	c.2646+27C>T		intron_variant		2		ENSP00000360885	A2

Frequencies

GnomAD3 genomes AF: 0.0727 AC: 11063 AN: 152150 Hom.: 428 Cov.: 33

Gnomad AFR AF: 0.0698

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0567

Gnomad ASJ AF: 0.0703

Gnomad EAS AF: 0.0366

Gnomad SAS AF: 0.0424

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0789

Gnomad OTH AF: 0.0867

GnomAD3 exomes AF: 0.0704 AC: 15907 AN: 226060 Hom.: 591 AF XY: 0.0706 AC XY: 8614 AN XY: 121984

Gnomad AFR exome AF: 0.0748

Gnomad AMR exome AF: 0.0487

Gnomad ASJ exome AF: 0.0613

Gnomad EAS exome AF: 0.0410

Gnomad SAS exome AF: 0.0454

Gnomad FIN exome AF: 0.102

Gnomad NFE exome AF: 0.0828

Gnomad OTH exome AF: 0.0736

GnomAD4 exome AF: 0.0716 AC: 103200 AN: 1441244 Hom.: 3839 Cov.: 29 AF XY: 0.0711 AC XY: 50936 AN XY: 716094

Gnomad4 AFR exome AF: 0.0712

Gnomad4 AMR exome AF: 0.0493

Gnomad4 ASJ exome AF: 0.0636

Gnomad4 EAS exome AF: 0.0273

Gnomad4 SAS exome AF: 0.0441

Gnomad4 FIN exome AF: 0.0988

Gnomad4 NFE exome AF: 0.0751

Gnomad4 OTH exome AF: 0.0721

GnomAD4 genome AF: 0.0727 AC: 11076 AN: 152268 Hom.: 430 Cov.: 33 AF XY: 0.0724 AC XY: 5388 AN XY: 74462

Gnomad4 AFR AF: 0.0700

Gnomad4 AMR AF: 0.0567

Gnomad4 ASJ AF: 0.0703

Gnomad4 EAS AF: 0.0366

Gnomad4 SAS AF: 0.0425

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.0789

Gnomad4 OTH AF: 0.0858

Alfa AF: 0.0766 Hom.: 100

Bravo AF: 0.0704

Asia WGS AF: 0.0550 AC: 190 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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -

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

- -

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	-0.91
CADD	Benign	1.0
DANN	Benign	0.84

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: rs13301426; hg19: chr9-137677921;