Variant 13-110307358-C-T 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.-215C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 260,090 control chromosomes in the GnomAD database, including 31,514 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 18514 hom., cov: 32)

Exomes 𝑓: 0.49 ( 13000 hom. )

Consequence

COL4A2
NM_001846.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -3.06

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=-0.82).

BP6

Variant 13-110307358-C-T is Benign according to our data. Variant chr13-110307358-C-T is described in ClinVar as [Benign]. Clinvar id is 311091.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.576 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.-215C>T		5_prime_UTR_variant	1/48	ENST00000360467.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A2	ENST00000360467.7 linkuse as main transcript	c.-215C>T		5_prime_UTR_variant	1/48	5	NM_001846.4	P1

Frequencies

GnomAD3 genomes

AF:

0.492

AC:

74481

AN:

151502

Hom.:

18486

Cov.:

show subpopulations

Gnomad AFR

AF:

0.478

Gnomad AMI

AF:

0.513

Gnomad AMR

AF:

0.585

Gnomad ASJ

AF:

0.472

Gnomad EAS

AF:

0.532

Gnomad SAS

AF:

0.529

Gnomad FIN

AF:

0.497

Gnomad MID

AF:

0.529

Gnomad NFE

AF:

0.473

Gnomad OTH

AF:

0.488

GnomAD4 exome

AF:

0.488

AC:

52921

AN:

108478

Hom.:

13000

Cov.:

AF XY:

0.492

AC XY:

26818

AN XY:

54536

show subpopulations

Gnomad4 AFR exome

AF:

0.472

Gnomad4 AMR exome

AF:

0.620

Gnomad4 ASJ exome

AF:

0.462

Gnomad4 EAS exome

AF:

0.584

Gnomad4 SAS exome

AF:

0.522

Gnomad4 FIN exome

AF:

0.494

Gnomad4 NFE exome

AF:

0.471

Gnomad4 OTH exome

AF:

0.486

GnomAD4 genome

AF:

0.492

AC:

74557

AN:

151612

Hom.:

18514

Cov.:

AF XY:

0.496

AC XY:

36765

AN XY:

74056

show subpopulations

Gnomad4 AFR

AF:

0.478

Gnomad4 AMR

AF:

0.586

Gnomad4 ASJ

AF:

0.472

Gnomad4 EAS

AF:

0.533

Gnomad4 SAS

AF:

0.531

Gnomad4 FIN

AF:

0.497

Gnomad4 NFE

AF:

0.473

Gnomad4 OTH

AF:

0.490

Alfa

AF:

0.476

Hom.:

2148

Bravo

AF:

0.495

Asia WGS

AF:

0.494

AC:

1699

AN:

3440

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 17, 2021	- -

Brain small vessel disease 1 with or without ocular anomalies

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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. -

Porencephalic cyst

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.4

DANN

Benign

0.80

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