Variant 13-110457323-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001846.4(COL4A2):c.1340-20A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00819 in 1,330,752 control chromosomes in the GnomAD database, including 521 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 142 hom., cov: 31)

Exomes 𝑓: 0.0071 ( 379 hom. )

Consequence

COL4A2
NM_001846.4 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.99

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:

COL4A2-AS2 (HGNC:39849): (COL4A2 antisense RNA 2)

COL4A2-AS2 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=-0.9).

BP6

Variant 13-110457323-A-C is Benign according to our data. Variant chr13-110457323-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 1213127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110457323-A-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0184 (2387/129608) while in subpopulation AFR AF= 0.0264 (881/33354). AF 95% confidence interval is 0.025. There are 142 homozygotes in gnomad4. There are 1168 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2387 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A2	NM_001846.4 link	c.1340-20A>C		intron_variant		ENST00000360467.7	NP_001837.2	P08572A0A024RDW8
COL4A2-AS2	NR_171022.1 link	n.595T>G		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
COL4A2	ENST00000360467.7 link	c.1340-20A>C	intron_variant		5	NM_001846.4	ENSP00000353654.5	P08572
COL4A2	ENST00000617564.2 link	c.596-20A>C	intron_variant		6		ENSP00000481492.3	A0A087WY39
COL4A2-AS2	ENST00000458403.2 link	n.595T>G	non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes

AF:

0.0184

AC:

2385

AN:

129506

Hom.:

143

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0264

Gnomad AMI

AF:

0.00225

Gnomad AMR

AF:

0.0164

Gnomad ASJ

AF:

0.0253

Gnomad EAS

AF:

0.0265

Gnomad SAS

AF:

0.0200

Gnomad FIN

AF:

0.0136

Gnomad MID

AF:

0.0500

Gnomad NFE

AF:

0.0142

Gnomad OTH

AF:

0.0198

GnomAD3 exomes

AF:

0.0106

AC:

2222

AN:

209454

Hom.:

133

AF XY:

0.00919

AC XY:

1048

AN XY:

114020

show subpopulations

Gnomad AFR exome

AF:

0.0157

Gnomad AMR exome

AF:

0.0136

Gnomad ASJ exome

AF:

0.00813

Gnomad EAS exome

AF:

0.0251

Gnomad SAS exome

AF:

0.00758

Gnomad FIN exome

AF:

0.0124

Gnomad NFE exome

AF:

0.00757

Gnomad OTH exome

AF:

0.0112

GnomAD4 exome

AF:

0.00709

AC:

8518

AN:

1201144

Hom.:

379

Cov.:

AF XY:

0.00789

AC XY:

4751

AN XY:

602208

show subpopulations

Gnomad4 AFR exome

AF:

0.0122

Gnomad4 AMR exome

AF:

0.0172

Gnomad4 ASJ exome

AF:

0.0131

Gnomad4 EAS exome

AF:

0.0165

Gnomad4 SAS exome

AF:

0.0201

Gnomad4 FIN exome

AF:

0.0129

Gnomad4 NFE exome

AF:

0.00447

Gnomad4 OTH exome

AF:

0.00883

GnomAD4 genome

AF:

0.0184

AC:

2387

AN:

129608

Hom.:

142

Cov.:

AF XY:

0.0184

AC XY:

1168

AN XY:

63340

show subpopulations

Gnomad4 AFR

AF:

0.0264

Gnomad4 AMR

AF:

0.0163

Gnomad4 ASJ

AF:

0.0253

Gnomad4 EAS

AF:

0.0261

Gnomad4 SAS

AF:

0.0205

Gnomad4 FIN

AF:

0.0136

Gnomad4 NFE

AF:

0.0142

Gnomad4 OTH

AF:

0.0196

Alfa

AF:

0.0589

Hom.:

120

Bravo

AF:

0.0991

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

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

-0.90

CADD

Benign

1.4

DANN

Benign

0.30

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