9-134728628-C-T

Position:

• chr9-134728628-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.787-42C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 1,611,774 control chromosomes in the GnomAD database, including 163,584 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (13446 hom., cov: 33)
  • Exomes 𝑓: 0.45 (150138 hom.)
• Consequence: COL5A1 NM_000093.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.41

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 9-134728628-C-T is Benign according to our data. Variant chr9-134728628-C-T is described in ClinVar as [Benign]. Clinvar id is 255100.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL5A1	NM_000093.5	c.787-42C>T		intron_variant		ENST00000371817.8	NP_000084.3
COL5A1	NM_001278074.1	c.787-42C>T		intron_variant			NP_001265003.1
COL5A1	XM_017014266.3	c.787-42C>T		intron_variant			XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8	c.787-42C>T		intron_variant		1	NM_000093.5	ENSP00000360882.3
COL5A1	ENST00000371820.4	c.787-42C>T		intron_variant		2		ENSP00000360885.4

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60927 AN: 151930 Hom.: 13429 Cov.: 33

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.335

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.450

GnomAD3 exomes AF: 0.480 AC: 120009 AN: 250212 Hom.: 30666 AF XY: 0.476 AC XY: 64470 AN XY: 135380

Gnomad AFR exome AF: 0.204

Gnomad AMR exome AF: 0.709

Gnomad ASJ exome AF: 0.627

Gnomad EAS exome AF: 0.466

Gnomad SAS exome AF: 0.471

Gnomad FIN exome AF: 0.465

Gnomad NFE exome AF: 0.443

Gnomad OTH exome AF: 0.489

GnomAD4 exome AF: 0.448 AC: 654597 AN: 1459726 Hom.: 150138 Cov.: 38 AF XY: 0.449 AC XY: 326277 AN XY: 726224

Gnomad4 AFR exome AF: 0.207

Gnomad4 AMR exome AF: 0.694

Gnomad4 ASJ exome AF: 0.628

Gnomad4 EAS exome AF: 0.470

Gnomad4 SAS exome AF: 0.471

Gnomad4 FIN exome AF: 0.463

Gnomad4 NFE exome AF: 0.438

Gnomad4 OTH exome AF: 0.454

GnomAD4 genome AF: 0.401 AC: 60979 AN: 152048 Hom.: 13446 Cov.: 33 AF XY: 0.409 AC XY: 30399 AN XY: 74300

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.576

Gnomad4 ASJ AF: 0.626

Gnomad4 EAS AF: 0.481

Gnomad4 SAS AF: 0.468

Gnomad4 FIN AF: 0.462

Gnomad4 NFE AF: 0.439

Gnomad4 OTH AF: 0.453

Alfa AF: 0.440 Hom.: 2873

Bravo AF: 0.402

Asia WGS AF: 0.509 AC: 1764 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 14, 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

Jul 30, 2021

- -

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	0.046
DANN	Benign	0.91

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: rs3124302; hg19: chr9-137620474; COSMIC: COSV65677079; COSMIC: COSV65677079;