Variant 20-874330-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_015985.4(ANGPT4):c.1305A>C(p.Ser435Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00607 in 1,614,190 control chromosomes in the GnomAD database, including 179 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 39 hom., cov: 32)

Exomes 𝑓: 0.0050 ( 140 hom. )

Consequence

ANGPT4
NM_015985.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.31

Variant links:

Genes affected

ANGPT4 (HGNC:487): (angiopoietin 4) Angiopoietins are proteins with important roles in vascular development and angiogenesis. All angiopoietins bind with similar affinity to an endothelial cell-specific tyrosine-protein kinase receptor. The mechanism by which they contribute to angiogenesis is thought to involve regulation of endothelial cell interactions with supporting perivascular cells. The protein encoded by this gene functions as an agonist and is an angiopoietin. [provided by RefSeq, Jul 2008]

ANGPT4 links:

LOC124904854 (HGNC:):

LOC124904854 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

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

BP6

Variant 20-874330-T-G is Benign according to our data. Variant chr20-874330-T-G is described in ClinVar as [Benign]. Clinvar id is 771934.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.31 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.016 (2443/152312) while in subpopulation AFR AF= 0.0397 (1649/41562). AF 95% confidence interval is 0.0381. There are 39 homozygotes in gnomad4. There are 1226 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 39 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANGPT4	NM_015985.4 linkuse as main transcript	c.1305A>C	p.Ser435Ser	synonymous_variant	8/9	ENST00000381922.5	NP_057069.1	Q9Y264-1
ANGPT4	XM_011529239.4 linkuse as main transcript	c.1149A>C	p.Ser383Ser	synonymous_variant	7/8		XP_011527541.1
ANGPT4	NM_001322809.2 linkuse as main transcript	c.1221-1210A>C		intron_variant			NP_001309738.1	Q9Y264-2
LOC124904854	XR_007067485.1 linkuse as main transcript	n.1329+189T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANGPT4	ENST00000381922.5 linkuse as main transcript	c.1305A>C	p.Ser435Ser	synonymous_variant	8/9	1	NM_015985.4	ENSP00000371347.3		Q9Y264-1

Frequencies

GnomAD3 genomes

AF:

0.0160

AC:

2438

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0396

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0119

Gnomad ASJ

AF:

0.0651

Gnomad EAS

AF:

0.00520

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.0121

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00257

Gnomad OTH

AF:

0.0220

GnomAD3 exomes

AF:

0.00968

AC:

2434

AN:

251420

Hom.:

AF XY:

0.00853

AC XY:

1159

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.0380

Gnomad AMR exome

AF:

0.00894

Gnomad ASJ exome

AF:

0.0703

Gnomad EAS exome

AF:

0.00337

Gnomad SAS exome

AF:

0.00121

Gnomad FIN exome

AF:

0.0107

Gnomad NFE exome

AF:

0.00338

Gnomad OTH exome

AF:

0.0137

GnomAD4 exome

AF:

0.00504

AC:

7363

AN:

1461878

Hom.:

140

Cov.:

AF XY:

0.00485

AC XY:

3529

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0411

Gnomad4 AMR exome

AF:

0.00928

Gnomad4 ASJ exome

AF:

0.0692

Gnomad4 EAS exome

AF:

0.00290

Gnomad4 SAS exome

AF:

0.00117

Gnomad4 FIN exome

AF:

0.00940

Gnomad4 NFE exome

AF:

0.00192

Gnomad4 OTH exome

AF:

0.0127

GnomAD4 genome

AF:

0.0160

AC:

2443

AN:

152312

Hom.:

Cov.:

AF XY:

0.0165

AC XY:

1226

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0397

Gnomad4 AMR

AF:

0.0118

Gnomad4 ASJ

AF:

0.0651

Gnomad4 EAS

AF:

0.00521

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.0121

Gnomad4 NFE

AF:

0.00256

Gnomad4 OTH

AF:

0.0213

Alfa

AF:

0.0125

Hom.:

Bravo

AF:

0.0173

Asia WGS

AF:

0.00982

AC:

AN:

3478

EpiCase

AF:

0.00349

EpiControl

AF:

0.00480

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 20, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.43

DANN

Benign

0.36

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