rs10858286

Positions:

• chr9-134838538-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

LOC101448202 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL5A1	NM_000093.5	c.5370+3334C>T		intron_variant		ENST00000371817.8	NP_000084.3
LOC101448202	NR_103451.2	n.71-18329G>A		intron_variant, non_coding_transcript_variant
COL5A1	NM_001278074.1	c.5370+3334C>T		intron_variant			NP_001265003.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8	c.5370+3334C>T		intron_variant		1	NM_000093.5	ENSP00000360882	P4
COL5A1	ENST00000371820.4	c.5370+3334C>T		intron_variant		2		ENSP00000360885	A2

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

Gnomad4 AFR AF: 0.436

Gnomad4 AMR AF: 0.475

Gnomad4 ASJ AF: 0.621

Gnomad4 EAS AF: 0.384

Gnomad4 SAS AF: 0.555

Gnomad4 FIN AF: 0.535

Gnomad4 NFE AF: 0.638

Gnomad4 OTH AF: 0.547

Alfa AF: 0.621 Hom.: 31805

Bravo AF: 0.533

Asia WGS AF: 0.469 AC: 1628 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.27
DANN	Benign	0.57

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: rs10858286; hg19: chr9-137730384; COSMIC: COSV65667232; COSMIC: COSV65667232;