9-99067260-G-A

Variant names:

• chr9-99067260-G-A
• rs1537504
• NM_001855.5:c.3837+193G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001855.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL15A1	NM_001855.5	MANE Select	c.3837+193G>A		intron	N/A	NP_001846.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL15A1	ENST00000375001.8	TSL:1 MANE Select	c.3837+193G>A		intron	N/A	ENSP00000364140.3

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

African (AFR) AF: 0.320 AC: 13274 AN: 41422

American (AMR) AF: 0.320 AC: 4892 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 824 AN: 3470

East Asian (EAS) AF: 0.601 AC: 3100 AN: 5154

South Asian (SAS) AF: 0.451 AC: 2170 AN: 4816

European-Finnish (FIN) AF: 0.171 AC: 1808 AN: 10574

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.226 AC: 15332 AN: 67974

Other (OTH) AF: 0.298 AC: 629 AN: 2114

Alfa AF: 0.244 Hom.: 2563

Bravo AF: 0.291

Asia WGS AF: 0.505 AC: 1753 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	5.6
DANN	Benign	0.77
PhyloP100		0.16
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: rs1537504; hg19: chr9-101829542;