NM_001666.5:c.67+1770G>A

Variant names:

• chrX-153924366-C-T
• rs2269368
• NM_001666.5:c.67+1770G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 publications found

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 Gene-Disease associations (from GenCC):

• intellectual disability

  Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001666.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP4	NM_001666.5	MANE Select	c.67+1770G>A		intron	N/A	NP_001657.3
	ARHGAP4	NM_001164741.2		c.67+1770G>A		intron	N/A	NP_001158213.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP4	ENST00000350060.10	TSL:1 MANE Select	c.67+1770G>A		intron	N/A	ENSP00000203786.8
	ARHGAP4	ENST00000370028.7	TSL:1	c.67+1770G>A		intron	N/A	ENSP00000359045.3
	ARHGAP4	ENST00000370016.5	TSL:5	c.67+1770G>A		intron	N/A	ENSP00000359033.1

Frequencies

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

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

African (AFR) AF: 0.538 AC: 16310 AN: 30295

American (AMR) AF: 0.420 AC: 4390 AN: 10446

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 623 AN: 2634

East Asian (EAS) AF: 0.658 AC: 2268 AN: 3447

South Asian (SAS) AF: 0.514 AC: 1356 AN: 2639

European-Finnish (FIN) AF: 0.137 AC: 818 AN: 5984

Middle Eastern (MID) AF: 0.299 AC: 64 AN: 214

European-Non Finnish (NFE) AF: 0.135 AC: 7149 AN: 52889

Other (OTH) AF: 0.340 AC: 514 AN: 1512

Alfa AF: 0.219 Hom.: 15538

Bravo AF: 0.339

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.68
PhyloP100		-0.62
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2269368; hg19: chrX-153189819;