chr9-98985750-G-T

Variant names:

• chr9-98985750-G-T
• rs370081942
• NM_001855.5:c.286G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001855.5(COL15A1):​c.286G>T​(p.Val96Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V96M) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: COL15A1 NM_001855.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.52
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05479455).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL15A1	NM_001855.5	c.286G>T	p.Val96Leu	missense_variant	Exon 3 of 42	ENST00000375001.8	NP_001846.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL15A1	ENST00000375001.8	c.286G>T	p.Val96Leu	missense_variant	Exon 3 of 42	1	NM_001855.5	ENSP00000364140.3
COL15A1	ENST00000471477.1	n.709G>T		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	11
DANN	Benign	0.50
DEOGEN2	Benign	0.10	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.50	N
LIST_S2	Benign	0.14	T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.055	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.69	N;.
PhyloP100		3.5
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.72	N;.
REVEL	Benign	0.18
Sift	Benign	0.67	T;.
Sift4G	Benign	0.49	T;T
Polyphen		0.0010	B;.
Vest4		0.040
MutPred		0.51		Gain of loop (P = 0.069);.;
MVP		0.45
MPC		0.071
ClinPred		0.068	T
GERP RS		1.1
Varity_R		0.047
gMVP		0.30
Mutation Taster		=99/1	polymorphism

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: rs370081942; hg19: chr9-101748032;