rs5978435

Variant names:

• chrX-11415973-T-C
• rs5978435
• NM_013427.3:c.589-161266A>G

Variant summary

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

The NM_013427.3(ARHGAP6):​c.589-161266A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 111,185 control chromosomes in the GnomAD database, including 1,737 homozygotes. There are 6,496 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 0.20 (1737 hom., 6496 hem., cov: 23)
• Consequence: ARHGAP6 NM_013427.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.734

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP6	NM_013427.3	c.589-161266A>G		intron_variant	Intron 1 of 12	ENST00000337414.9	NP_038286.2
ARHGAP6	NM_001287242.2	c.48+11575A>G		intron_variant	Intron 1 of 12		NP_001274171.1
ARHGAP6	NM_006125.3	c.589-161266A>G		intron_variant	Intron 1 of 10		NP_006116.2
ARHGAP6	NR_109776.2	n.1681-125495A>G		intron_variant	Intron 1 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP6	ENST00000337414.9	c.589-161266A>G		intron_variant	Intron 1 of 12	1	NM_013427.3	ENSP00000338967.4

Frequencies

GnomAD3 genomes AF: 0.200 AC: 22183 AN: 111132 Hom.: 1740 Cov.: 23 AF XY: 0.195 AC XY: 6493 AN XY: 33356

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.0399

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.321

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.200 AC: 22186 AN: 111185 Hom.: 1737 Cov.: 23 AF XY: 0.194 AC XY: 6496 AN XY: 33419

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.0400

Gnomad4 SAS AF: 0.185

Gnomad4 FIN AF: 0.307

Gnomad4 NFE AF: 0.241

Gnomad4 OTH AF: 0.204

Alfa AF: 0.229 Hom.: 12607

Bravo AF: 0.184

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.1
DANN	Benign	0.63

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: rs5978435; hg19: chrX-11434093;