rs3929758

chr13-110429810-C-Achr13-110429810-C-G

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.478-75C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.732 in 1,468,696 control chromosomes in the GnomAD database, including 394,946 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.75 (42870 hom., cov: 32)
  • Exomes 𝑓: 0.73 (352076 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.22

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=-0.93).
• BP6: Variant 13-110429810-C-A is Benign according to our data. Variant chr13-110429810-C-A is described in ClinVar as [Benign]. Clinvar id is 1241415.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A2	NM_001846.4	c.478-75C>A		intron_variant		ENST00000360467.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A2	ENST00000360467.7	c.478-75C>A		intron_variant		5	NM_001846.4	P1
COL4A2	ENST00000619688.2	c.*1176C>A		3_prime_UTR_variant	3/3
COL4A2	ENST00000650540.1	c.478-75C>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.749 AC: 113849 AN: 151960 Hom.: 42837 Cov.: 32

Gnomad AFR AF: 0.808

Gnomad AMI AF: 0.833

Gnomad AMR AF: 0.720

Gnomad ASJ AF: 0.742

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.724

Gnomad FIN AF: 0.786

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.726

Gnomad OTH AF: 0.746

GnomAD4 exome AF: 0.730 AC: 961520 AN: 1316618 Hom.: 352076 AF XY: 0.730 AC XY: 482769 AN XY: 661046

Gnomad4 AFR exome AF: 0.811

Gnomad4 AMR exome AF: 0.661

Gnomad4 ASJ exome AF: 0.759

Gnomad4 EAS exome AF: 0.613

Gnomad4 SAS exome AF: 0.723

Gnomad4 FIN exome AF: 0.776

Gnomad4 NFE exome AF: 0.732

Gnomad4 OTH exome AF: 0.734

GnomAD4 genome AF: 0.749 AC: 113939 AN: 152078 Hom.: 42870 Cov.: 32 AF XY: 0.751 AC XY: 55813 AN XY: 74342

Gnomad4 AFR AF: 0.808

Gnomad4 AMR AF: 0.720

Gnomad4 ASJ AF: 0.742

Gnomad4 EAS AF: 0.608

Gnomad4 SAS AF: 0.724

Gnomad4 FIN AF: 0.786

Gnomad4 NFE AF: 0.726

Gnomad4 OTH AF: 0.744

Alfa AF: 0.722 Hom.: 12429

Bravo AF: 0.746

Asia WGS AF: 0.688 AC: 2394 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	-0.93
Cadd	Benign	0.045
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: rs3929758; hg19: chr13-111082157;