rs7319311

Positions:

• chr13-110378231-A-G

Variant summary

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

The NM_001846.4(COL4A2):​c.180+20679A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 152,136 control chromosomes in the GnomAD database, including 9,226 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 0.34 (9226 hom., cov: 33)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.722

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A2	NM_001846.4	c.180+20679A>G		intron_variant		ENST00000360467.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A2	ENST00000360467.7	c.180+20679A>G		intron_variant		5	NM_001846.4	P1
COL4A2	ENST00000400163.7	c.180+20679A>G		intron_variant		5
COL4A2	ENST00000650540.1	c.180+20679A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52260 AN: 152018 Hom.: 9211 Cov.: 33

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.314

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

GnomAD4 genome AF: 0.344 AC: 52343 AN: 152136 Hom.: 9226 Cov.: 33 AF XY: 0.339 AC XY: 25215 AN XY: 74362

Gnomad4 AFR AF: 0.421

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.388

Gnomad4 SAS AF: 0.257

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.321

Gnomad4 OTH AF: 0.314

Alfa AF: 0.321 Hom.: 18357

Bravo AF: 0.350

Asia WGS AF: 0.333 AC: 1157 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.39
DANN	Benign	0.45

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: rs7319311; hg19: chr13-111030578;