X-153924366-C-T

Position:

• chrX-153924366-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001666.5(ARHGAP4):​c.67+1770G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 110,743 control chromosomes in the GnomAD database, including 5,082 homozygotes. There are 10,011 hemizygotes in GnomAD. 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: 𝑓 0.30 (5082 hom., 10011 hem., cov: 22)
• Consequence: ARHGAP4 NM_001666.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.621

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP4	NM_001666.5	c.67+1770G>A		intron_variant		ENST00000350060.10	NP_001657.3
ARHGAP4	NM_001164741.2	c.67+1770G>A		intron_variant			NP_001158213.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP4	ENST00000350060.10	c.67+1770G>A		intron_variant		1	NM_001666.5	ENSP00000203786.8

Frequencies

GnomAD3 genomes AF: 0.302 AC: 33451 AN: 110686 Hom.: 5083 Cov.: 22 AF XY: 0.302 AC XY: 9966 AN XY: 32970

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.00586

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.658

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.340

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.302 AC: 33496 AN: 110743 Hom.: 5082 Cov.: 22 AF XY: 0.303 AC XY: 10011 AN XY: 33037

Gnomad4 AFR AF: 0.538

Gnomad4 AMR AF: 0.420

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.658

Gnomad4 SAS AF: 0.514

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.340

Alfa AF: 0.189 Hom.: 8447

Bravo AF: 0.339

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.68

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

Other links and lift over

dbSNP: rs2269368; hg19: chrX-153189819;