Variant rs74967960 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.315+19T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0094 in 1,614,086 control chromosomes in the GnomAD database, including 245 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 92 hom., cov: 34)

Exomes 𝑓: 0.0078 ( 153 hom. )

Consequence

COL4A2
NM_001846.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.11

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

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 13-110424887-T-C is Benign according to our data. Variant chr13-110424887-T-C is described in ClinVar as [Benign]. Clinvar id is 1280685.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110424887-T-C is described in Lovd as [Benign]. Variant chr13-110424887-T-C is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A2	NM_001846.4 linkuse as main transcript	c.315+19T>C		intron_variant		ENST00000360467.7

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
COL4A2	ENST00000360467.7 linkuse as main transcript	c.315+19T>C	intron_variant	5	NM_001846.4	P1
COL4A2	ENST00000619688.2 linkuse as main transcript	c.67+19T>C	intron_variant
COL4A2	ENST00000650540.1 linkuse as main transcript	c.315+19T>C	intron_variant
COL4A2	ENST00000400163.7 linkuse as main transcript		downstream_gene_variant	5

Frequencies

GnomAD3 genomes

AF:

0.0248

AC:

3770

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0716

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0107

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00424

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00800

Gnomad OTH

AF:

0.0158

GnomAD3 exomes

AF:

0.00944

AC:

2355

AN:

249500

Hom.:

AF XY:

0.00796

AC XY:

1077

AN XY:

135368

show subpopulations

Gnomad AFR exome

AF:

0.0778

Gnomad AMR exome

AF:

0.00562

Gnomad ASJ exome

AF:

0.00129

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000392

Gnomad FIN exome

AF:

0.00478

Gnomad NFE exome

AF:

0.00700

Gnomad OTH exome

AF:

0.00578

GnomAD4 exome

AF:

0.00780

AC:

11402

AN:

1461814

Hom.:

153

Cov.:

AF XY:

0.00750

AC XY:

5455

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.0742

Gnomad4 AMR exome

AF:

0.00561

Gnomad4 ASJ exome

AF:

0.00119

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000591

Gnomad4 FIN exome

AF:

0.00498

Gnomad4 NFE exome

AF:

0.00690

Gnomad4 OTH exome

AF:

0.0102

GnomAD4 genome

AF:

0.0248

AC:

3774

AN:

152272

Hom.:

Cov.:

AF XY:

0.0244

AC XY:

1818

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0715

Gnomad4 AMR

AF:

0.0106

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00424

Gnomad4 NFE

AF:

0.00800

Gnomad4 OTH

AF:

0.0156

Alfa

AF:

0.0152

Hom.:

Bravo

AF:

0.0270

Asia WGS

AF:

0.00722

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 25, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 10, 2018	- -

not specified

Benign:1

Benign, no assertion criteria provided

clinical testing

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.066

DANN

Benign

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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