rs3128591

Variant names:

• chr9-134710273-G-A
• rs3128591
• NM_000093.5:c.654+8940G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-134710273-G-A
• chr9-134710273-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000093.5(COL5A1):​c.654+8940G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 152,220 control chromosomes in the GnomAD database, including 40,193 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.72 (40193 hom., cov: 35)
• Consequence: COL5A1 NM_000093.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0630
• Publications: 4 publications found

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]

COL5A1 Gene-Disease associations (from GenCC):

• Ehlers-Danlos syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• Ehlers-Danlos syndrome, classic type

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Ambry Genetics, PanelApp Australia, Genomics England PanelApp
• Ehlers-Danlos syndrome, classic type, 1

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• arterial disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL5A1	NM_000093.5	c.654+8940G>A		intron_variant	Intron 4 of 65	ENST00000371817.8	NP_000084.3
COL5A1	NM_001278074.1	c.654+8940G>A		intron_variant	Intron 4 of 65		NP_001265003.1
COL5A1	XM_017014266.3	c.654+8940G>A		intron_variant	Intron 4 of 64		XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8	c.654+8940G>A		intron_variant	Intron 4 of 65	1	NM_000093.5	ENSP00000360882.3
COL5A1	ENST00000371820.4	c.654+8940G>A		intron_variant	Intron 4 of 65	2		ENSP00000360885.4

Frequencies

GnomAD3 genomes AF: 0.724 AC: 110143 AN: 152102 Hom.: 40155 Cov.: 35

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.796

Gnomad ASJ AF: 0.831

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.748

Gnomad OTH AF: 0.739

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.724 AC: 110239 AN: 152220 Hom.: 40193 Cov.: 35 AF XY: 0.723 AC XY: 53792 AN XY: 74422

African (AFR) AF: 0.685 AC: 28466 AN: 41546

American (AMR) AF: 0.796 AC: 12187 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.831 AC: 2884 AN: 3470

East Asian (EAS) AF: 0.598 AC: 3083 AN: 5158

South Asian (SAS) AF: 0.592 AC: 2855 AN: 4826

European-Finnish (FIN) AF: 0.728 AC: 7717 AN: 10604

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.748 AC: 50831 AN: 67994

Other (OTH) AF: 0.738 AC: 1560 AN: 2114

Alfa AF: 0.742 Hom.: 100400

Bravo AF: 0.728

Asia WGS AF: 0.649 AC: 2253 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.93
PhyloP100		-0.063
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3128591; hg19: chr9-137602119;