rs56385965

Positions:

• chr9-134731688-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.1332+25C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 1,596,236 control chromosomes in the GnomAD database, including 37,503 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3285 hom., cov: 34)
  • Exomes 𝑓: 0.21 (34218 hom.)
• Consequence: COL5A1 NM_000093.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.837

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 9-134731688-C-T is Benign according to our data. Variant chr9-134731688-C-T is described in ClinVar as [Benign]. Clinvar id is 255048.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL5A1	NM_000093.5	c.1332+25C>T		intron_variant		ENST00000371817.8	NP_000084.3
COL5A1	NM_001278074.1	c.1332+25C>T		intron_variant			NP_001265003.1
COL5A1	XM_017014266.3	c.1332+25C>T		intron_variant			XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8	c.1332+25C>T		intron_variant		1	NM_000093.5	ENSP00000360882	P4
COL5A1	ENST00000371820.4	c.1332+25C>T		intron_variant		2		ENSP00000360885	A2
COL5A1	ENST00000469093.1	n.71+25C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30421 AN: 152012 Hom.: 3285 Cov.: 34

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.195

GnomAD3 exomes AF: 0.221 AC: 51647 AN: 233964 Hom.: 6649 AF XY: 0.228 AC XY: 29074 AN XY: 127546

Gnomad AFR exome AF: 0.182

Gnomad AMR exome AF: 0.119

Gnomad ASJ exome AF: 0.123

Gnomad EAS exome AF: 0.447

Gnomad SAS exome AF: 0.326

Gnomad FIN exome AF: 0.233

Gnomad NFE exome AF: 0.199

Gnomad OTH exome AF: 0.197

GnomAD4 exome AF: 0.210 AC: 303821 AN: 1444106 Hom.: 34218 Cov.: 35 AF XY: 0.214 AC XY: 153203 AN XY: 716114

Gnomad4 AFR exome AF: 0.171

Gnomad4 AMR exome AF: 0.123

Gnomad4 ASJ exome AF: 0.122

Gnomad4 EAS exome AF: 0.435

Gnomad4 SAS exome AF: 0.324

Gnomad4 FIN exome AF: 0.226

Gnomad4 NFE exome AF: 0.200

Gnomad4 OTH exome AF: 0.209

GnomAD4 genome AF: 0.200 AC: 30418 AN: 152130 Hom.: 3285 Cov.: 34 AF XY: 0.204 AC XY: 15153 AN XY: 74386

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.157

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.196

Alfa AF: 0.179 Hom.: 477

Bravo AF: 0.194

Asia WGS AF: 0.316 AC: 1101 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 26, 2018	- -
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

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	0.65
DANN	Benign	0.72

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: rs56385965; hg19: chr9-137623534; COSMIC: COSV65673666;