rs5978433

Variant names:

• chrX-11359151-T-C
• rs5978433
• NM_013427.3:c.589-104444A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013427.3(ARHGAP6):​c.589-104444A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 111,252 control chromosomes in the GnomAD database, including 1,509 homozygotes. There are 5,784 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 0.18 (1509 hom., 5784 hem., cov: 23)
• Consequence: ARHGAP6 NM_013427.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35
• Publications: 2 publications found

Genes affected

ARHGAP6 (HGNC:676): (Rho GTPase activating protein 6) This gene encodes a member of the rhoGAP family of proteins which play a role in the regulation of actin polymerization at the plasma membrane during several cellular processes. This protein is thought to have two independent functions, one as a GTPase-activating protein with specificity for RhoA, and another as a cytoskeletal protein that promotes actin remodeling. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013427.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP6	NM_013427.3	MANE Select	c.589-104444A>G		intron	N/A	NP_038286.2	O43182-1
	ARHGAP6	NM_001287242.2		c.48+68397A>G		intron	N/A	NP_001274171.1
	ARHGAP6	NM_006125.3		c.589-104444A>G		intron	N/A	NP_006116.2	O43182-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP6	ENST00000337414.9	TSL:1 MANE Select	c.589-104444A>G		intron	N/A	ENSP00000338967.4	O43182-1
	ARHGAP6	ENST00000380736.5	TSL:1	c.-22+68397A>G		intron	N/A	ENSP00000370112.1	O43182-4
	ARHGAP6	ENST00000380718.1	TSL:1	c.589-104444A>G		intron	N/A	ENSP00000370094.1	O43182-2

Frequencies

GnomAD3 genomes AF: 0.179 AC: 19955 AN: 111198 Hom.: 1511 Cov.: 23

Gnomad AFR AF: 0.0945

Gnomad AMI AF: 0.0988

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.0384

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.179 AC: 19954 AN: 111252 Hom.: 1509 Cov.: 23 AF XY: 0.173 AC XY: 5784 AN XY: 33480

African (AFR) AF: 0.0943 AC: 2902 AN: 30783

American (AMR) AF: 0.123 AC: 1290 AN: 10480

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 682 AN: 2632

East Asian (EAS) AF: 0.0388 AC: 138 AN: 3559

South Asian (SAS) AF: 0.175 AC: 463 AN: 2647

European-Finnish (FIN) AF: 0.294 AC: 1718 AN: 5850

Middle Eastern (MID) AF: 0.315 AC: 67 AN: 213

European-Non Finnish (NFE) AF: 0.234 AC: 12356 AN: 52885

Other (OTH) AF: 0.178 AC: 271 AN: 1525

Alfa AF: 0.204 Hom.: 15993

Bravo AF: 0.164

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.4
DANN	Benign	0.74
PhyloP100		1.4
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: rs5978433; hg19: chrX-11377271;