dbSNP rs34734302: COL4A2:c.1189+47A>G (chr13-110449836-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_001846.4(COL4A2):c.1189+47A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 1,522,806 control chromosomes in the GnomAD database, including 182,792 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 16684 hom., cov: 32)

Exomes 𝑓: 0.49 ( 166108 hom. )

Consequence

COL4A2
NM_001846.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -5.67

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 13-110449836-A-G is Benign according to our data. Variant chr13-110449836-A-G is described in ClinVar as [Benign]. Clinvar id is 1249478.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4 link	c.1189+47A>G		intron_variant	Intron 19 of 47	ENST00000360467.7	NP_001837.2	P08572A0A024RDW8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7 link	c.1189+47A>G		intron_variant	Intron 19 of 47	5	NM_001846.4	ENSP00000353654.5		P08572
COL4A2	ENST00000617564.2 link	c.445+47A>G		intron_variant	Intron 7 of 9	6		ENSP00000481492.3		A0A087WY39

Frequencies

GnomAD3 genomes

AF:

0.466

AC:

70720

AN:

151796

Hom.:

16662

Cov.:

show subpopulations

Gnomad AFR

AF:

0.448

Gnomad AMI

AF:

0.555

Gnomad AMR

AF:

0.385

Gnomad ASJ

AF:

0.373

Gnomad EAS

AF:

0.319

Gnomad SAS

AF:

0.490

Gnomad FIN

AF:

0.526

Gnomad MID

AF:

0.334

Gnomad NFE

AF:

0.500

Gnomad OTH

AF:

0.432

GnomAD3 exomes

AF:

0.452

AC:

62855

AN:

139184

Hom.:

14555

AF XY:

0.457

AC XY:

34285

AN XY:

74988

show subpopulations

Gnomad AFR exome

AF:

0.450

Gnomad AMR exome

AF:

0.352

Gnomad ASJ exome

AF:

0.358

Gnomad EAS exome

AF:

0.317

Gnomad SAS exome

AF:

0.489

Gnomad FIN exome

AF:

0.533

Gnomad NFE exome

AF:

0.499

Gnomad OTH exome

AF:

0.432

GnomAD4 exome

AF:

0.489

AC:

670917

AN:

1370892

Hom.:

166108

Cov.:

AF XY:

0.490

AC XY:

331798

AN XY:

677174

show subpopulations

Gnomad4 AFR exome

AF:

0.446

Gnomad4 AMR exome

AF:

0.350

Gnomad4 ASJ exome

AF:

0.352

Gnomad4 EAS exome

AF:

0.322

Gnomad4 SAS exome

AF:

0.488

Gnomad4 FIN exome

AF:

0.534

Gnomad4 NFE exome

AF:

0.504

Gnomad4 OTH exome

AF:

0.466

GnomAD4 genome

AF:

0.466

AC:

70766

AN:

151914

Hom.:

16684

Cov.:

AF XY:

0.467

AC XY:

34675

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.449

Gnomad4 AMR

AF:

0.384

Gnomad4 ASJ

AF:

0.373

Gnomad4 EAS

AF:

0.320

Gnomad4 SAS

AF:

0.491

Gnomad4 FIN

AF:

0.526

Gnomad4 NFE

AF:

0.500

Gnomad4 OTH

AF:

0.427

Alfa

AF:

0.468

Hom.:

3376

Bravo

AF:

0.447

Asia WGS

AF:

0.406

AC:

1417

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 29, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.040

DANN

Benign

0.16

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