Variant 13-110512918-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001846.4(COL4A2):c.*727G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 151,878 control chromosomes in the GnomAD database, including 15,104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.44 ( 15098 hom., cov: 31)

Exomes 𝑓: 0.46 ( 6 hom. )

Consequence

COL4A2
NM_001846.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.169

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 13-110512918-G-C is Benign according to our data. Variant chr13-110512918-G-C is described in ClinVar as [Benign]. Clinvar id is 311214.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.733 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.*727G>C		3_prime_UTR_variant	48/48	ENST00000360467.7

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
COL4A2	ENST00000360467.7 linkuse as main transcript	c.*727G>C	3_prime_UTR_variant	48/48	5	NM_001846.4	P1
COL4A2	ENST00000648222.1 linkuse as main transcript	n.1554G>C	non_coding_transcript_exon_variant	1/1
COL4A2	ENST00000650225.1 linkuse as main transcript	n.3521G>C	non_coding_transcript_exon_variant	19/19

Frequencies

GnomAD3 genomes

AF:

0.440

AC:

66823

AN:

151706

Hom.:

15090

Cov.:

show subpopulations

Gnomad AFR

AF:

0.351

Gnomad AMI

AF:

0.523

Gnomad AMR

AF:

0.431

Gnomad ASJ

AF:

0.431

Gnomad EAS

AF:

0.752

Gnomad SAS

AF:

0.559

Gnomad FIN

AF:

0.532

Gnomad MID

AF:

0.392

Gnomad NFE

AF:

0.450

Gnomad OTH

AF:

0.431

GnomAD4 exome

AF:

0.463

AC:

AN:

Hom.:

Cov.:

AF XY:

0.475

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

1.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.500

Gnomad4 SAS exome

AF:

0.750

Gnomad4 FIN exome

AF:

0.667

Gnomad4 NFE exome

AF:

0.344

Gnomad4 OTH exome

AF:

0.667

GnomAD4 genome

AF:

0.440

AC:

66865

AN:

151824

Hom.:

15098

Cov.:

AF XY:

0.448

AC XY:

33195

AN XY:

74172

show subpopulations

Gnomad4 AFR

AF:

0.351

Gnomad4 AMR

AF:

0.431

Gnomad4 ASJ

AF:

0.431

Gnomad4 EAS

AF:

0.753

Gnomad4 SAS

AF:

0.557

Gnomad4 FIN

AF:

0.532

Gnomad4 NFE

AF:

0.450

Gnomad4 OTH

AF:

0.437

Alfa

AF:

0.314

Hom.:

866

Bravo

AF:

0.429

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Porencephaly 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.4

DANN

Benign

0.43

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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