rs10123014

Positions:

• chr9-134753802-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000371817.8(COL5A1):​c.1720-48T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 1,307,150 control chromosomes in the GnomAD database, including 54,072 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (5657 hom., cov: 26)
  • Exomes 𝑓: 0.29 (48415 hom.)
• Consequence: COL5A1 ENST00000371817.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.619

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 9-134753802-T-C is Benign according to our data. Variant chr9-134753802-T-C is described in ClinVar as [Benign]. Clinvar id is 255056.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL5A1	NM_000093.5	c.1720-48T>C		intron_variant		ENST00000371817.8	NP_000084.3
COL5A1	NM_001278074.1	c.1720-48T>C		intron_variant			NP_001265003.1
COL5A1	XM_017014266.3	c.1720-48T>C		intron_variant			XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8	c.1720-48T>C		intron_variant		1	NM_000093.5	ENSP00000360882	P4
COL5A1	ENST00000371820.4	c.1720-48T>C		intron_variant		2		ENSP00000360885	A2

Frequencies

GnomAD3 genomes AF: 0.275 AC: 40426 AN: 147064 Hom.: 5647 Cov.: 26

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.271

GnomAD3 exomes AF: 0.253 AC: 62763 AN: 248174 Hom.: 8382 AF XY: 0.253 AC XY: 34115 AN XY: 134620

Gnomad AFR exome AF: 0.288

Gnomad AMR exome AF: 0.147

Gnomad ASJ exome AF: 0.158

Gnomad EAS exome AF: 0.360

Gnomad SAS exome AF: 0.206

Gnomad FIN exome AF: 0.274

Gnomad NFE exome AF: 0.281

Gnomad OTH exome AF: 0.241

GnomAD4 exome AF: 0.289 AC: 334996 AN: 1159964 Hom.: 48415 Cov.: 17 AF XY: 0.286 AC XY: 168099 AN XY: 588378

Gnomad4 AFR exome AF: 0.300

Gnomad4 AMR exome AF: 0.160

Gnomad4 ASJ exome AF: 0.176

Gnomad4 EAS exome AF: 0.384

Gnomad4 SAS exome AF: 0.211

Gnomad4 FIN exome AF: 0.290

Gnomad4 NFE exome AF: 0.302

Gnomad4 OTH exome AF: 0.284

GnomAD4 genome AF: 0.275 AC: 40449 AN: 147186 Hom.: 5657 Cov.: 26 AF XY: 0.271 AC XY: 19455 AN XY: 71682

Gnomad4 AFR AF: 0.286

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.358

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.276

Gnomad4 NFE AF: 0.286

Gnomad4 OTH AF: 0.268

Alfa AF: 0.258 Hom.: 969

Bravo AF: 0.271

Asia WGS AF: 0.232 AC: 807 AN: 3476

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 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. -
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	2.4
DANN	Benign	0.35

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: rs10123014; hg19: chr9-137645648; COSMIC: COSV65670621;