13-110328660-C-G

Position:

• chr13-110328660-C-G

Variant summary

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

The NM_001846.4(COL4A2):​c.99+20537C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 152,028 control chromosomes in the GnomAD database, including 10,785 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 0.36 (10783 hom., cov: 32)
  • Exomes 𝑓: 0.45 (2 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0930

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.99+20537C>G		intron_variant		ENST00000360467.7	NP_001837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.99+20537C>G		intron_variant		5	NM_001846.4	ENSP00000353654	P1
COL4A2	ENST00000400163.7	c.99+20537C>G		intron_variant		5		ENSP00000383027
COL4A2	ENST00000649101.1	c.99+20537C>G		intron_variant				ENSP00000497869
COL4A2	ENST00000650540.1	c.99+20537C>G		intron_variant				ENSP00000497878

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54406 AN: 151888 Hom.: 10778 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.320

GnomAD4 exome AF: 0.455 AC: 10 AN: 22 Hom.: 2 AF XY: 0.400 AC XY: 8 AN XY: 20

Gnomad4 NFE exome AF: 0.450

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.358 AC: 54447 AN: 152006 Hom.: 10783 Cov.: 32 AF XY: 0.361 AC XY: 26854 AN XY: 74296

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.334

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.361

Gnomad4 FIN AF: 0.515

Gnomad4 NFE AF: 0.442

Gnomad4 OTH AF: 0.319

Alfa AF: 0.277 Hom.: 808

Bravo AF: 0.334

Asia WGS AF: 0.325 AC: 1130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.38

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: rs9521695; hg19: chr13-110981007;