Variant chr13-110456904-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001846.4(COL4A2):c.1340-439G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00304 in 135,420 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0030 ( 0 hom., cov: 22)

Exomes 𝑓: 0.00038 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

COL4A2
NM_001846.4 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.74

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 13-110456904-G-A is Benign according to our data. Variant chr13-110456904-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2643948.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00304 (412/135420) while in subpopulation NFE AF= 0.00458 (283/61776). AF 95% confidence interval is 0.00414. There are 0 homozygotes in gnomad4. There are 192 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High AC in GnomAd4 at 412 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A2	NM_001846.4 link	c.1340-439G>A		intron_variant		ENST00000360467.7	NP_001837.2	P08572A0A024RDW8
COL4A2-AS2	NR_171022.1 link	n.1014C>T		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
COL4A2	ENST00000360467.7 link	c.1340-439G>A	intron_variant		5	NM_001846.4	ENSP00000353654.5	P08572
COL4A2	ENST00000617564.2 link	c.596-439G>A	intron_variant		6		ENSP00000481492.3	A0A087WY39
COL4A2-AS2	ENST00000458403.2 link	n.1014C>T	non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes

AF:

0.00305

AC:

413

AN:

135348

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000870

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00218

Gnomad ASJ

AF:

0.0122

Gnomad EAS

AF:

0.000695

Gnomad SAS

AF:

0.00158

Gnomad FIN

AF:

0.00148

Gnomad MID

AF:

0.00407

Gnomad NFE

AF:

0.00458

Gnomad OTH

AF:

0.00318

GnomAD3 exomes

AF:

0.000176

AC:

AN:

125258

Hom.:

AF XY:

0.000192

AC XY:

AN XY:

67744

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000896

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000206

Gnomad FIN exome

AF:

0.000682

Gnomad NFE exome

AF:

0.000154

Gnomad OTH exome

AF:

0.000527

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000375

AC:

117

AN:

311804

Hom.:

Cov.:

AF XY:

0.000329

AC XY:

AN XY:

176154

show subpopulations

Gnomad4 AFR exome

AF:

0.000111

Gnomad4 AMR exome

AF:

0.000154

Gnomad4 ASJ exome

AF:

0.000456

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000470

Gnomad4 FIN exome

AF:

0.000419

Gnomad4 NFE exome

AF:

0.000411

Gnomad4 OTH exome

AF:

0.000268

GnomAD4 genome

AF:

0.00304

AC:

412

AN:

135420

Hom.:

Cov.:

AF XY:

0.00292

AC XY:

192

AN XY:

65750

show subpopulations

Gnomad4 AFR

AF:

0.000868

Gnomad4 AMR

AF:

0.00210

Gnomad4 ASJ

AF:

0.0122

Gnomad4 EAS

AF:

0.000697

Gnomad4 SAS

AF:

0.00159

Gnomad4 FIN

AF:

0.00148

Gnomad4 NFE

AF:

0.00458

Gnomad4 OTH

AF:

0.00316

Alfa

AF:

0.00582

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

COL4A2: BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.0

DANN

Uncertain

0.99

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