9-134810354-G-C

Position:

• chr9-134810354-G-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.3528+46G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 1,591,546 control chromosomes in the GnomAD database, including 177,342 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (17048 hom., cov: 34)
  • Exomes 𝑓: 0.47 (160294 hom.)
• Consequence: COL5A1 NM_000093.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.183

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 9-134810354-G-C is Benign according to our data. Variant chr9-134810354-G-C is described in ClinVar as [Benign]. Clinvar id is 255081.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL5A1	NM_000093.5	c.3528+46G>C		intron_variant		ENST00000371817.8	NP_000084.3
COL5A1	NM_001278074.1	c.3528+46G>C		intron_variant			NP_001265003.1
COL5A1	XM_017014266.3	c.3528+46G>C		intron_variant			XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8	c.3528+46G>C		intron_variant		1	NM_000093.5	ENSP00000360882	P4
COL5A1	ENST00000371820.4	c.3528+46G>C		intron_variant		2		ENSP00000360885	A2
COL5A1	ENST00000463925.1	n.430G>C		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71776 AN: 151742 Hom.: 17021 Cov.: 34

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.498

GnomAD3 exomes AF: 0.455 AC: 112431 AN: 246950 Hom.: 25638 AF XY: 0.455 AC XY: 60944 AN XY: 134020

Gnomad AFR exome AF: 0.505

Gnomad AMR exome AF: 0.385

Gnomad ASJ exome AF: 0.455

Gnomad EAS exome AF: 0.477

Gnomad SAS exome AF: 0.416

Gnomad FIN exome AF: 0.447

Gnomad NFE exome AF: 0.478

Gnomad OTH exome AF: 0.468

GnomAD4 exome AF: 0.471 AC: 677744 AN: 1439686 Hom.: 160294 Cov.: 27 AF XY: 0.470 AC XY: 336308 AN XY: 716064

Gnomad4 AFR exome AF: 0.506

Gnomad4 AMR exome AF: 0.388

Gnomad4 ASJ exome AF: 0.452

Gnomad4 EAS exome AF: 0.454

Gnomad4 SAS exome AF: 0.415

Gnomad4 FIN exome AF: 0.448

Gnomad4 NFE exome AF: 0.479

Gnomad4 OTH exome AF: 0.475

GnomAD4 genome AF: 0.473 AC: 71847 AN: 151860 Hom.: 17048 Cov.: 34 AF XY: 0.468 AC XY: 34772 AN XY: 74230

Gnomad4 AFR AF: 0.497

Gnomad4 AMR AF: 0.417

Gnomad4 ASJ AF: 0.448

Gnomad4 EAS AF: 0.463

Gnomad4 SAS AF: 0.404

Gnomad4 FIN AF: 0.448

Gnomad4 NFE AF: 0.480

Gnomad4 OTH AF: 0.499

Alfa AF: 0.411 Hom.: 1967

Bravo AF: 0.476

Asia WGS AF: 0.457 AC: 1592 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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 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	0.16
DANN	Benign	0.37

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: rs3827850; hg19: chr9-137702200;