rs1537504

Positions:

• chr9-99067260-G-A
• chr9-99067260-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001855.5(COL15A1):​c.3837+193G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 151,996 control chromosomes in the GnomAD database, including 6,452 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 0.28 (6452 hom., cov: 31)
• Consequence: COL15A1 NM_001855.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.162

Genes affected

COL15A1 (HGNC:2192): (collagen type XV alpha 1 chain) This gene encodes the alpha chain of type XV collagen, a member of the FACIT collagen family (fibril-associated collagens with interrupted helices). Type XV collagen has a wide tissue distribution but the strongest expression is localized to basement membrane zones so it may function to adhere basement membranes to underlying connective tissue stroma. The proteolytically produced C-terminal fragment of type XV collagen is restin, a potentially antiangiogenic protein that is closely related to endostatin. Mouse studies have shown that collagen XV deficiency is associated with muscle and microvessel deterioration. [provided by RefSeq, May 2013]

COL15A1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL15A1	NM_001855.5	c.3837+193G>A		intron_variant		ENST00000375001.8	NP_001846.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL15A1	ENST00000375001.8	c.3837+193G>A		intron_variant		1	NM_001855.5	ENSP00000364140.3
COL15A1	ENST00000610452.1	c.3795+193G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42259 AN: 151878 Hom.: 6447 Cov.: 31

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.601

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.298

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

GnomAD4 genome AF: 0.278 AC: 42284 AN: 151996 Hom.: 6452 Cov.: 31 AF XY: 0.280 AC XY: 20795 AN XY: 74298

Gnomad4 AFR AF: 0.320

Gnomad4 AMR AF: 0.320

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.601

Gnomad4 SAS AF: 0.451

Gnomad4 FIN AF: 0.171

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.298

Alfa AF: 0.247 Hom.: 2374

Bravo AF: 0.291

Asia WGS AF: 0.505 AC: 1753 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	5.6
DANN	Benign	0.77

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: rs1537504; hg19: chr9-101829542;