9-99061045-G-A

Position:

• chr9-99061045-G-A

Variant summary

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

The NM_001855.5(COL15A1):​c.3403-926G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,180 control chromosomes in the GnomAD database, including 2,577 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 0.17 (2577 hom., cov: 32)
• Consequence: COL15A1 NM_001855.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL15A1	NM_001855.5	c.3403-926G>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.3403-926G>A		intron_variant		1	NM_001855.5	ENSP00000364140	P1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25540 AN: 152062 Hom.: 2576 Cov.: 32

Gnomad AFR AF: 0.0417

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.168 AC: 25546 AN: 152180 Hom.: 2577 Cov.: 32 AF XY: 0.169 AC XY: 12542 AN XY: 74390

Gnomad4 AFR AF: 0.0416

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.223

Gnomad4 EAS AF: 0.235

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.191

Alfa AF: 0.211 Hom.: 6200

Bravo AF: 0.161

Asia WGS AF: 0.230 AC: 800 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.3
DANN	Benign	0.53

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: rs1360686; hg19: chr9-101823327;