Variant X-153909539-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001666.5(ARHGAP4):c.2415-4G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 1,199,563 control chromosomes in the GnomAD database, including 81 homozygotes. There are 4,398 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0089 ( 2 hom., 263 hem., cov: 26)

Exomes 𝑓: 0.012 ( 79 hom. 4135 hem. )

Consequence

ARHGAP4
NM_001666.5 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00002170

Clinical Significance

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

Conservation

PhyloP100: 0.142

Variant links:

Genes affected

ARHGAP4 (HGNC:674): (Rho GTPase activating protein 4) This gene encodes a member of the rhoGAP family of proteins which play a role in the regulation of small GTP-binding proteins belonging to the RAS superfamily. The protein encoded by the orthologous gene in rat is localized to the Golgi complex and can redistribute to microtubules. The rat protein stimulates the activity of some Rho GTPases in vitro. Genomic deletions of this gene and a neighboring gene have been found in patients with nephrogenic diabetes insipidus. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

ARHGAP4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant X-153909539-C-T is Benign according to our data. Variant chrX-153909539-C-T is described in ClinVar as [Benign]. Clinvar id is 771947.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-153909539-C-T is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP4	NM_001666.5 linkuse as main transcript	c.2415-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000350060.10	NP_001657.3
ARHGAP4	NM_001164741.2 linkuse as main transcript	c.2535-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_001158213.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP4	ENST00000350060.10 linkuse as main transcript	c.2415-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001666.5	ENSP00000203786	P2	P98171-1

Frequencies

GnomAD3 genomes

AF:

0.00888

AC:

992

AN:

111676

Hom.:

Cov.:

AF XY:

0.00780

AC XY:

264

AN XY:

33842

show subpopulations

Gnomad AFR

AF:

0.00176

Gnomad AMI

AF:

0.00293

Gnomad AMR

AF:

0.00537

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00879

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0150

Gnomad OTH

AF:

0.0113

GnomAD3 exomes

AF:

0.00802

AC:

1326

AN:

165238

Hom.:

AF XY:

0.00680

AC XY:

365

AN XY:

53714

show subpopulations

Gnomad AFR exome

AF:

0.00138

Gnomad AMR exome

AF:

0.00520

Gnomad ASJ exome

AF:

0.00446

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000619

Gnomad FIN exome

AF:

0.0122

Gnomad NFE exome

AF:

0.0128

Gnomad OTH exome

AF:

0.00909

GnomAD4 exome

AF:

0.0119

AC:

12976

AN:

1087832

Hom.:

Cov.:

AF XY:

0.0116

AC XY:

4135

AN XY:

354962

show subpopulations

Gnomad4 AFR exome

AF:

0.00183

Gnomad4 AMR exome

AF:

0.00551

Gnomad4 ASJ exome

AF:

0.00584

Gnomad4 EAS exome

AF:

0.0000664

Gnomad4 SAS exome

AF:

0.000134

Gnomad4 FIN exome

AF:

0.0123

Gnomad4 NFE exome

AF:

0.0139

Gnomad4 OTH exome

AF:

0.0102

GnomAD4 genome

AF:

0.00888

AC:

992

AN:

111731

Hom.:

Cov.:

AF XY:

0.00776

AC XY:

263

AN XY:

33907

show subpopulations

Gnomad4 AFR

AF:

0.00175

Gnomad4 AMR

AF:

0.00537

Gnomad4 ASJ

AF:

0.00605

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00879

Gnomad4 NFE

AF:

0.0150

Gnomad4 OTH

AF:

0.0111

Alfa

AF:

0.00721

Hom.:

Bravo

AF:

0.00770

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	Dec 31, 2019	- -
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

-0.81

CADD

Benign

0.74

DANN

Benign

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000022

dbscSNV1_RF

Benign

0.0020

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