rs10858286

Variant names:

• chr9-134838538-C-T
• rs10858286
• NM_000093.5:c.5370+3334C>T

Variant summary

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

The NM_000093.5(COL5A1):​c.5370+3334C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 151,998 control chromosomes in the GnomAD database, including 23,412 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 0.55 (23412 hom., cov: 32)
• Consequence: COL5A1 NM_000093.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.21
• Publications: 3 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: Genomics England PanelApp, Ambry Genetics, ClinGen, Orphanet
• 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

LOC101448202 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000093.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL5A1	NM_000093.5	MANE Select	c.5370+3334C>T		intron	N/A	NP_000084.3
	COL5A1	NM_001278074.1		c.5370+3334C>T		intron	N/A	NP_001265003.1	P20908-2
	LOC101448202	NR_103451.2		n.71-18329G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL5A1	ENST00000371817.8	TSL:1 MANE Select	c.5370+3334C>T		intron	N/A	ENSP00000360882.3	P20908-1
	COL5A1	ENST00000371820.4	TSL:2	c.5370+3334C>T		intron	N/A	ENSP00000360885.4	P20908-2
	COL5A1	ENST00000950240.1		c.5361+3334C>T		intron	N/A	ENSP00000620299.1

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82972 AN: 151880 Hom.: 23412 Cov.: 32

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.547

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

GnomAD4 genome AF: 0.546 AC: 82987 AN: 151998 Hom.: 23412 Cov.: 32 AF XY: 0.537 AC XY: 39917 AN XY: 74278

African (AFR) AF: 0.436 AC: 18088 AN: 41480

American (AMR) AF: 0.475 AC: 7246 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.621 AC: 2153 AN: 3468

East Asian (EAS) AF: 0.384 AC: 1977 AN: 5148

South Asian (SAS) AF: 0.555 AC: 2672 AN: 4816

European-Finnish (FIN) AF: 0.535 AC: 5652 AN: 10564

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.638 AC: 43332 AN: 67946

Other (OTH) AF: 0.547 AC: 1152 AN: 2106

Alfa AF: 0.611 Hom.: 52560

Bravo AF: 0.533

Asia WGS AF: 0.469 AC: 1628 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.27
DANN	Benign	0.57
PhyloP100		-2.2
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: rs10858286; hg19: chr9-137730384; COSMIC: COSV65667232; COSMIC: COSV65667232;