9-99052344-C-G

Variant names:

• chr9-99052344-C-G
• rs4142986
• NM_001855.5:c.2905-44C>G

Variant summary

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

The NM_001855.5(COL15A1):​c.2905-44C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.707 in 1,486,732 control chromosomes in the GnomAD database, including 377,430 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 0.77 (46669 hom., cov: 33)
  • Exomes 𝑓: 0.70 (330761 hom.)
• Consequence: COL15A1 NM_001855.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.477
• Publications: 8 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL15A1	NM_001855.5	c.2905-44C>G		intron_variant	Intron 30 of 41	ENST00000375001.8	NP_001846.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL15A1	ENST00000375001.8	c.2905-44C>G		intron_variant	Intron 30 of 41	1	NM_001855.5	ENSP00000364140.3

Frequencies

GnomAD3 genomes AF: 0.773 AC: 117631 AN: 152082 Hom.: 46605 Cov.: 33

Gnomad AFR AF: 0.943

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.783

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.908

Gnomad SAS AF: 0.770

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.680

Gnomad OTH AF: 0.744

GnomAD2 exomes AF: 0.747 AC: 187200 AN: 250764 AF XY: 0.736

Gnomad AFR exome AF: 0.950

Gnomad AMR exome AF: 0.857

Gnomad ASJ exome AF: 0.629

Gnomad EAS exome AF: 0.906

Gnomad FIN exome AF: 0.697

Gnomad NFE exome AF: 0.677

Gnomad OTH exome AF: 0.715

GnomAD4 exome AF: 0.700 AC: 933595 AN: 1334532 Hom.: 330761 Cov.: 20 AF XY: 0.699 AC XY: 469188 AN XY: 671342

African (AFR) AF: 0.952 AC: 29462 AN: 30944

American (AMR) AF: 0.851 AC: 37891 AN: 44538

Ashkenazi Jewish (ASJ) AF: 0.625 AC: 15841 AN: 25358

East Asian (EAS) AF: 0.933 AC: 36490 AN: 39100

South Asian (SAS) AF: 0.753 AC: 62925 AN: 83610

European-Finnish (FIN) AF: 0.696 AC: 37090 AN: 53286

Middle Eastern (MID) AF: 0.667 AC: 3499 AN: 5248

European-Non Finnish (NFE) AF: 0.673 AC: 670058 AN: 996214

Other (OTH) AF: 0.717 AC: 40339 AN: 56234

GnomAD4 genome AF: 0.774 AC: 117757 AN: 152200 Hom.: 46669 Cov.: 33 AF XY: 0.773 AC XY: 57489 AN XY: 74404

African (AFR) AF: 0.943 AC: 39181 AN: 41562

American (AMR) AF: 0.783 AC: 11974 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.630 AC: 2184 AN: 3468

East Asian (EAS) AF: 0.908 AC: 4695 AN: 5168

South Asian (SAS) AF: 0.770 AC: 3707 AN: 4814

European-Finnish (FIN) AF: 0.700 AC: 7414 AN: 10596

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.680 AC: 46198 AN: 67984

Other (OTH) AF: 0.746 AC: 1577 AN: 2114

Alfa AF: 0.651 Hom.: 3809

Bravo AF: 0.789

Asia WGS AF: 0.870 AC: 3028 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.55
DANN	Benign	0.41
PhyloP100		-0.48
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: rs4142986; hg19: chr9-101814626; COSMIC: COSV66641456;