Variant rs7326449 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001846.4(COL4A2):c.1012-23G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 1,602,554 control chromosomes in the GnomAD database, including 499,541 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.74 ( 42633 hom., cov: 31)

Exomes 𝑓: 0.79 ( 456908 hom. )

Consequence

COL4A2
NM_001846.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.64

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 13-110446775-G-A is Benign according to our data. Variant chr13-110446775-G-A is described in ClinVar as [Benign]. Clinvar id is 1217364.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110446775-G-A is described in Lovd as [Benign].

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	Protein	UniProt
COL4A2	NM_001846.4 linkuse as main transcript	c.1012-23G>A		intron_variant		ENST00000360467.7	NP_001837.2	P08572A0A024RDW8

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
COL4A2	ENST00000360467.7 linkuse as main transcript	c.1012-23G>A	intron_variant	5	NM_001846.4	ENSP00000353654.5	P08572
COL4A2	ENST00000650540.1 linkuse as main transcript	c.1012-23G>A	intron_variant			ENSP00000497878.1	A0A3B3ITQ8
COL4A2	ENST00000617564.2 linkuse as main transcript	c.268-23G>A	intron_variant	6		ENSP00000481492.3	A0A087WY39

Frequencies

GnomAD3 genomes

AF:

0.745

AC:

113150

AN:

151942

Hom.:

42613

Cov.:

show subpopulations

Gnomad AFR

AF:

0.657

Gnomad AMI

AF:

0.890

Gnomad AMR

AF:

0.732

Gnomad ASJ

AF:

0.869

Gnomad EAS

AF:

0.603

Gnomad SAS

AF:

0.717

Gnomad FIN

AF:

0.685

Gnomad MID

AF:

0.880

Gnomad NFE

AF:

0.813

Gnomad OTH

AF:

0.779

GnomAD3 exomes

AF:

0.746

AC:

185483

AN:

248700

Hom.:

70167

AF XY:

0.752

AC XY:

101462

AN XY:

134996

show subpopulations

Gnomad AFR exome

AF:

0.657

Gnomad AMR exome

AF:

0.659

Gnomad ASJ exome

AF:

0.867

Gnomad EAS exome

AF:

0.594

Gnomad SAS exome

AF:

0.718

Gnomad FIN exome

AF:

0.695

Gnomad NFE exome

AF:

0.813

Gnomad OTH exome

AF:

0.775

GnomAD4 exome

AF:

0.791

AC:

1147819

AN:

1450494

Hom.:

456908

Cov.:

AF XY:

0.791

AC XY:

570153

AN XY:

720548

show subpopulations

Gnomad4 AFR exome

AF:

0.657

Gnomad4 AMR exome

AF:

0.665

Gnomad4 ASJ exome

AF:

0.867

Gnomad4 EAS exome

AF:

0.613

Gnomad4 SAS exome

AF:

0.721

Gnomad4 FIN exome

AF:

0.694

Gnomad4 NFE exome

AF:

0.815

Gnomad4 OTH exome

AF:

0.786

GnomAD4 genome

AF:

0.745

AC:

113213

AN:

152060

Hom.:

42633

Cov.:

AF XY:

0.737

AC XY:

54787

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.657

Gnomad4 AMR

AF:

0.732

Gnomad4 ASJ

AF:

0.869

Gnomad4 EAS

AF:

0.604

Gnomad4 SAS

AF:

0.718

Gnomad4 FIN

AF:

0.685

Gnomad4 NFE

AF:

0.813

Gnomad4 OTH

AF:

0.777

Alfa

AF:

0.799

Hom.:

26191

Bravo

AF:

0.743

Asia WGS

AF:

0.651

AC:

2267

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -

Porencephaly 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.0010

DANN

Benign

0.68

BranchPoint Hunter

1.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over