13-110401612-G-T

Position:

• chr13-110401612-G-T

Variant summary

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

The NM_001846.4(COL4A2):​c.181-23122G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 152,118 control chromosomes in the GnomAD database, including 26,969 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 0.59 (26969 hom., cov: 33)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.98

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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.181-23122G>T		intron_variant		ENST00000360467.7	NP_001837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.181-23122G>T		intron_variant		5	NM_001846.4	ENSP00000353654	P1
COL4A2	ENST00000400163.7	c.181-23122G>T		intron_variant		5		ENSP00000383027
COL4A2	ENST00000650540.1	c.181-23122G>T		intron_variant				ENSP00000497878

Frequencies

GnomAD3 genomes AF: 0.589 AC: 89529 AN: 152000 Hom.: 26969 Cov.: 33

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.707

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.551

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.662

Gnomad OTH AF: 0.570

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

GnomAD4 genome AF: 0.589 AC: 89565 AN: 152118 Hom.: 26969 Cov.: 33 AF XY: 0.585 AC XY: 43486 AN XY: 74358

Gnomad4 AFR AF: 0.460

Gnomad4 AMR AF: 0.653

Gnomad4 ASJ AF: 0.571

Gnomad4 EAS AF: 0.494

Gnomad4 SAS AF: 0.551

Gnomad4 FIN AF: 0.594

Gnomad4 NFE AF: 0.662

Gnomad4 OTH AF: 0.567

Alfa AF: 0.624 Hom.: 13604

Bravo AF: 0.589

Asia WGS AF: 0.529 AC: 1840 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.028
DANN	Benign	0.51

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: rs1927343; hg19: chr13-111053959;