13-110314002-G-T

Position:

• chr13-110314002-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.99+5879G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,204 control chromosomes in the GnomAD database, including 2,086 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 0.16 (2086 hom., cov: 33)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.19

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]

COL4A2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.99+5879G>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.99+5879G>T		intron_variant		5	NM_001846.4	ENSP00000353654.5

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24273 AN: 152086 Hom.: 2082 Cov.: 33

Gnomad AFR AF: 0.0982

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.141

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

GnomAD4 genome AF: 0.160 AC: 24293 AN: 152204 Hom.: 2086 Cov.: 33 AF XY: 0.163 AC XY: 12132 AN XY: 74404

Gnomad4 AFR AF: 0.0983

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.196

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.140

Alfa AF: 0.166 Hom.: 3029

Bravo AF: 0.157

Asia WGS AF: 0.213 AC: 741 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.36
DANN	Benign	0.34

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: rs9583484; hg19: chr13-110966349;