9-98998959-G-T

Variant names:

• chr9-98998959-G-T
• rs1413299
• NM_001855.5:c.952+1878G>T

Variant summary

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

The NM_001855.5(COL15A1):​c.952+1878G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 152,150 control chromosomes in the GnomAD database, including 19,488 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 0.49 (19488 hom., cov: 33)
• Consequence: COL15A1 NM_001855.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.318
• Publications: 23 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.679 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.952+1878G>T		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.952+1878G>T		intron	N/A	ENSP00000364140.3
	COL15A1	ENST00000946050.1		c.952+1878G>T		intron	N/A	ENSP00000616109.1
	COL15A1	ENST00000873223.1		c.967+1878G>T		intron	N/A	ENSP00000543282.1

Frequencies

GnomAD3 genomes AF: 0.487 AC: 74042 AN: 152030 Hom.: 19446 Cov.: 33

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.471

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

GnomAD4 genome AF: 0.487 AC: 74141 AN: 152150 Hom.: 19488 Cov.: 33 AF XY: 0.491 AC XY: 36511 AN XY: 74372

African (AFR) AF: 0.685 AC: 28449 AN: 41518

American (AMR) AF: 0.474 AC: 7244 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 1458 AN: 3472

East Asian (EAS) AF: 0.591 AC: 3049 AN: 5162

South Asian (SAS) AF: 0.538 AC: 2598 AN: 4828

European-Finnish (FIN) AF: 0.444 AC: 4706 AN: 10588

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.371 AC: 25233 AN: 67966

Other (OTH) AF: 0.472 AC: 996 AN: 2112

Alfa AF: 0.408 Hom.: 40885

Bravo AF: 0.501

Asia WGS AF: 0.644 AC: 2238 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.30
PhyloP100		-0.32
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: rs1413299; hg19: chr9-101761241;