Genetic Variant NM_001846.4:c.4285+71G>T (chr13-110504064-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001846.4(COL4A2):c.4285+71G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,407,992 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

COL4A2
NM_001846.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.40

Publications

0 publications found

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-AS1 (HGNC:40156): (COL4A2 antisense RNA 1)

COL4A2-AS1 links:

ENSG00000289010 (HGNC:):

ENSG00000289010 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4 link	c.4285+71G>T		intron_variant	Intron 44 of 47	ENST00000360467.7	NP_001837.2	P08572A0A024RDW8
COL4A2-AS1	NR_046583.1 link	n.187-1136C>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7 link	c.4285+71G>T		intron_variant	Intron 44 of 47	5	NM_001846.4	ENSP00000353654.5		P08572

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000142

AC:

AN:

1407992

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

702146

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32194

American (AMR)

AF:

0.00

AC:

AN:

43270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24826

East Asian (EAS)

AF:

0.00

AC:

AN:

39456

South Asian (SAS)

AF:

0.00

AC:

AN:

83518

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52526

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5548

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1068206

Other (OTH)

AF:

0.0000342

AC:

AN:

58448

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.057

(source)

DANN

Benign

0.68

PhyloP100

-3.4

PromoterAI

0.088

Neutral

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over