rs45612833

chr13-110446710-G-Achr13-110446710-G-Cchr13-110446710-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001846.4(COL4A2):c.1012-88G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.79 in 1,152,402 control chromosomes in the GnomAD database, including 362,391 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.75 (42904 hom., cov: 32)
  • Exomes 𝑓: 0.80 (319487 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.39

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 13-110446710-G-A is Benign according to our data. Variant chr13-110446710-G-A is described in ClinVar as [Benign]. Clinvar id is 1259552.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A2	NM_001846.4	c.1012-88G>A		intron_variant		ENST00000360467.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A2	ENST00000360467.7	c.1012-88G>A		intron_variant		5	NM_001846.4	P1
COL4A2	ENST00000617564.2	c.269-88G>A		intron_variant
COL4A2	ENST00000650540.1	c.1012-88G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.748 AC: 113567 AN: 151928 Hom.: 42883 Cov.: 32

Gnomad AFR AF: 0.666

Gnomad AMI AF: 0.890

Gnomad AMR AF: 0.734

Gnomad ASJ AF: 0.869

Gnomad EAS AF: 0.605

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.879

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.783

GnomAD4 exome AF: 0.796 AC: 796621 AN: 1000356 Hom.: 319487 AF XY: 0.796 AC XY: 404552 AN XY: 508520

Gnomad4 AFR exome AF: 0.678

Gnomad4 AMR exome AF: 0.663

Gnomad4 ASJ exome AF: 0.870

Gnomad4 EAS exome AF: 0.615

Gnomad4 SAS exome AF: 0.728

Gnomad4 FIN exome AF: 0.692

Gnomad4 NFE exome AF: 0.826

Gnomad4 OTH exome AF: 0.793

GnomAD4 genome AF: 0.747 AC: 113631 AN: 152046 Hom.: 42904 Cov.: 32 AF XY: 0.740 AC XY: 55005 AN XY: 74332

Gnomad4 AFR AF: 0.666

Gnomad4 AMR AF: 0.734

Gnomad4 ASJ AF: 0.869

Gnomad4 EAS AF: 0.606

Gnomad4 SAS AF: 0.720

Gnomad4 FIN AF: 0.686

Gnomad4 NFE AF: 0.813

Gnomad4 OTH AF: 0.781

Alfa AF: 0.794 Hom.: 9494

Bravo AF: 0.746

Asia WGS AF: 0.652 AC: 2271 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.0040
Dann	Benign	0.58

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: rs45612833; hg19: chr13-111099057;