rs5978433

Positions:

• chrX-11359151-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP6	NM_013427.3	c.589-104444A>G		intron_variant		ENST00000337414.9	NP_038286.2
ARHGAP6	NM_001287242.2	c.48+68397A>G		intron_variant			NP_001274171.1
ARHGAP6	NM_006125.3	c.589-104444A>G		intron_variant			NP_006116.2
ARHGAP6	NR_109776.2	n.1681-68673A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP6	ENST00000337414.9	c.589-104444A>G		intron_variant		1	NM_013427.3	ENSP00000338967	P2

Frequencies

GnomAD3 genomes AF: 0.179 AC: 19955 AN: 111198 Hom.: 1511 Cov.: 23 AF XY: 0.173 AC XY: 5784 AN XY: 33416

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

Gnomad4 AFR AF: 0.0943

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.0388

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.294

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.178

Alfa AF: 0.220 Hom.: 11762

Bravo AF: 0.164

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.4
DANN	Benign	0.74

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: rs5978433; hg19: chrX-11377271;