rs13297647

Positions:

• chr9-134810219-A-C

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.3475-36A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0483 in 1,612,244 control chromosomes in the GnomAD database, including 2,061 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.038 (144 hom., cov: 34)
  • Exomes 𝑓: 0.049 (1917 hom.)
• Consequence: COL5A1 NM_000093.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.104

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=-0.84).
• BP6: Variant 9-134810219-A-C is Benign according to our data. Variant chr9-134810219-A-C is described in ClinVar as [Benign]. Clinvar id is 255077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL5A1	NM_000093.5	c.3475-36A>C		intron_variant		ENST00000371817.8	NP_000084.3
COL5A1	NM_001278074.1	c.3475-36A>C		intron_variant			NP_001265003.1
COL5A1	XM_017014266.3	c.3475-36A>C		intron_variant			XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8	c.3475-36A>C		intron_variant		1	NM_000093.5	ENSP00000360882	P4
COL5A1	ENST00000371820.4	c.3475-36A>C		intron_variant		2		ENSP00000360885	A2
COL5A1	ENST00000463925.1	n.331-36A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0384 AC: 5849 AN: 152256 Hom.: 144 Cov.: 34

Gnomad AFR AF: 0.00945

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0268

Gnomad ASJ AF: 0.0458

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0174

Gnomad FIN AF: 0.0740

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0573

Gnomad OTH AF: 0.0339

GnomAD3 exomes AF: 0.0409 AC: 10269 AN: 251070 Hom.: 287 AF XY: 0.0411 AC XY: 5585 AN XY: 135798

Gnomad AFR exome AF: 0.00802

Gnomad AMR exome AF: 0.0185

Gnomad ASJ exome AF: 0.0411

Gnomad EAS exome AF: 0.000435

Gnomad SAS exome AF: 0.0181

Gnomad FIN exome AF: 0.0710

Gnomad NFE exome AF: 0.0591

Gnomad OTH exome AF: 0.0459

GnomAD4 exome AF: 0.0493 AC: 71950 AN: 1459870 Hom.: 1917 Cov.: 32 AF XY: 0.0486 AC XY: 35287 AN XY: 726394

Gnomad4 AFR exome AF: 0.00816

Gnomad4 AMR exome AF: 0.0202

Gnomad4 ASJ exome AF: 0.0408

Gnomad4 EAS exome AF: 0.000277

Gnomad4 SAS exome AF: 0.0171

Gnomad4 FIN exome AF: 0.0707

Gnomad4 NFE exome AF: 0.0555

Gnomad4 OTH exome AF: 0.0441

GnomAD4 genome AF: 0.0384 AC: 5848 AN: 152374 Hom.: 144 Cov.: 34 AF XY: 0.0382 AC XY: 2847 AN XY: 74520

Gnomad4 AFR AF: 0.00943

Gnomad4 AMR AF: 0.0268

Gnomad4 ASJ AF: 0.0458

Gnomad4 EAS AF: 0.000964

Gnomad4 SAS AF: 0.0176

Gnomad4 FIN AF: 0.0740

Gnomad4 NFE AF: 0.0573

Gnomad4 OTH AF: 0.0336

Alfa AF: 0.0463 Hom.: 36

Bravo AF: 0.0344

Asia WGS AF: 0.0150 AC: 52 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	-0.84
CADD	Benign	2.9
DANN	Benign	0.51

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: rs13297647; hg19: chr9-137702065;