dbSNP rs7984937: COL4A2:c.862-56T>C (chr13-110438562-T-C) – 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.862-56T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 1,607,394 control chromosomes in the GnomAD database, including 75,040 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 10398 hom., cov: 33)

Exomes 𝑓: 0.29 ( 64642 hom. )

Consequence

COL4A2
NM_001846.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.148

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=-0.91).

BP6

Variant 13-110438562-T-C is Benign according to our data. Variant chr13-110438562-T-C is described in ClinVar as [Benign]. Clinvar id is 1272751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110438562-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4 link	c.862-56T>C		intron_variant	Intron 14 of 47	ENST00000360467.7	NP_001837.2	P08572A0A024RDW8

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL4A2	ENST00000360467.7 link	c.862-56T>C	intron_variant	Intron 14 of 47	5	NM_001846.4	ENSP00000353654.5	P08572
COL4A2	ENST00000650540.1 link	c.862-56T>C	intron_variant	Intron 14 of 17			ENSP00000497878.1	A0A3B3ITQ8
COL4A2	ENST00000617564.2 link	c.118-56T>C	intron_variant	Intron 2 of 9	6		ENSP00000481492.3	A0A087WY39

Frequencies

GnomAD3 genomes

AF:

0.352

AC:

53397

AN:

151780

Hom.:

10391

Cov.:

show subpopulations

Gnomad AFR

AF:

0.531

Gnomad AMI

AF:

0.239

Gnomad AMR

AF:

0.293

Gnomad ASJ

AF:

0.429

Gnomad EAS

AF:

0.127

Gnomad SAS

AF:

0.207

Gnomad FIN

AF:

0.286

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.291

Gnomad OTH

AF:

0.353

GnomAD3 exomes

AF:

0.284

AC:

70880

AN:

249408

Hom.:

11379

AF XY:

0.282

AC XY:

38094

AN XY:

135322

show subpopulations

Gnomad AFR exome

AF:

0.543

Gnomad AMR exome

AF:

0.195

Gnomad ASJ exome

AF:

0.449

Gnomad EAS exome

AF:

0.145

Gnomad SAS exome

AF:

0.222

Gnomad FIN exome

AF:

0.294

Gnomad NFE exome

AF:

0.297

Gnomad OTH exome

AF:

0.306

GnomAD4 exome

AF:

0.290

AC:

422437

AN:

1455496

Hom.:

64642

Cov.:

AF XY:

0.288

AC XY:

208927

AN XY:

724546

show subpopulations

Gnomad4 AFR exome

AF:

0.540

Gnomad4 AMR exome

AF:

0.206

Gnomad4 ASJ exome

AF:

0.444

Gnomad4 EAS exome

AF:

0.116

Gnomad4 SAS exome

AF:

0.224

Gnomad4 FIN exome

AF:

0.289

Gnomad4 NFE exome

AF:

0.292

Gnomad4 OTH exome

AF:

0.313

GnomAD4 genome

AF:

0.352

AC:

53440

AN:

151898

Hom.:

10398

Cov.:

AF XY:

0.346

AC XY:

25709

AN XY:

74238

show subpopulations

Gnomad4 AFR

AF:

0.531

Gnomad4 AMR

AF:

0.292

Gnomad4 ASJ

AF:

0.429

Gnomad4 EAS

AF:

0.127

Gnomad4 SAS

AF:

0.207

Gnomad4 FIN

AF:

0.286

Gnomad4 NFE

AF:

0.291

Gnomad4 OTH

AF:

0.354

Alfa

AF:

0.321

Hom.:

2360

Bravo

AF:

0.364

Asia WGS

AF:

0.211

AC:

733

AN:

3476

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

- -

Jul 09, 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

-0.91

CADD

Benign

4.3

DANN

Benign

0.27

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