rs9515201

chr13-110388451-A-Cchr13-110388451-A-Gchr13-110388451-A-T

Variant summary

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

The NM_001846.4(COL4A2):c.180+30899A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 152,128 control chromosomes in the GnomAD database, including 32,601 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 0.64 (32601 hom., cov: 32)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.11

Genes affected

COL4A2 (HGNC:2203): (collagen type IV alpha 2 chain) This gene encodes one of the six subunits of type IV collagen, the major structural component of basement membranes. The C-terminal portion of the protein, known as canstatin, is an inhibitor of angiogenesis and tumor growth. Like the other members of the type IV collagen gene family, this gene is organized in a head-to-head conformation with another type IV collagen gene so that each gene pair shares a common promoter. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A2	NM_001846.4	c.180+30899A>C		intron_variant		ENST00000360467.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A2	ENST00000360467.7	c.180+30899A>C		intron_variant		5	NM_001846.4	P1
COL4A2	ENST00000400163.7	c.180+30899A>C		intron_variant		5
COL4A2	ENST00000650540.1	c.180+30899A>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97531 AN: 152010 Hom.: 32595 Cov.: 32

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.838

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.594

Gnomad EAS AF: 0.884

Gnomad SAS AF: 0.774

Gnomad FIN AF: 0.741

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.648

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

GnomAD4 genome AF: 0.641 AC: 97582 AN: 152128 Hom.: 32601 Cov.: 32 AF XY: 0.650 AC XY: 48323 AN XY: 74372

Gnomad4 AFR AF: 0.446

Gnomad4 AMR AF: 0.748

Gnomad4 ASJ AF: 0.594

Gnomad4 EAS AF: 0.884

Gnomad4 SAS AF: 0.773

Gnomad4 FIN AF: 0.741

Gnomad4 NFE AF: 0.693

Gnomad4 OTH AF: 0.646

Alfa AF: 0.685 Hom.: 48577

Bravo AF: 0.635

Asia WGS AF: 0.768 AC: 2668 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	18
Dann	Benign	0.52

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: rs9515201; hg19: chr13-111040798;