rs3859991

Positions:

• chrX-131088561-G-A
• chrX-131088561-G-C

Variant summary

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

The NM_144967.4(ARHGAP36):​c.1487-67G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0857 in 1,119,907 control chromosomes in the GnomAD database, including 3,811 homozygotes. There are 30,232 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 0.085 (445 hom., 2910 hem., cov: 23)
  • Exomes 𝑓: 0.086 (3366 hom. 27322 hem.)
• Consequence: ARHGAP36 NM_144967.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.818

Genes affected

ARHGAP36 (HGNC:26388): (Rho GTPase activating protein 36) Predicted to enable GTPase activator activity. Predicted to be involved in regulation of catalytic activity and signal transduction. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP36	NM_144967.4	c.1487-67G>A		intron_variant		ENST00000276211.10
ARHGAP36	NM_001282607.2	c.1451-67G>A		intron_variant
ARHGAP36	NM_001330651.1	c.1079-67G>A		intron_variant
ARHGAP36	XM_011531280.2	c.1079-67G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP36	ENST00000276211.10	c.1487-67G>A		intron_variant		2	NM_144967.4	P4

Frequencies

GnomAD3 genomes AF: 0.0849 AC: 9496 AN: 111822 Hom.: 442 Cov.: 23 AF XY: 0.0853 AC XY: 2901 AN XY: 34010

Gnomad AFR AF: 0.0558

Gnomad AMI AF: 0.0547

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.0547

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.0658

Gnomad MID AF: 0.0636

Gnomad NFE AF: 0.0703

Gnomad OTH AF: 0.114

GnomAD4 exome AF: 0.0858 AC: 86442 AN: 1008032 Hom.: 3366 AF XY: 0.0897 AC XY: 27322 AN XY: 304518

Gnomad4 AFR exome AF: 0.0603

Gnomad4 AMR exome AF: 0.320

Gnomad4 ASJ exome AF: 0.0589

Gnomad4 EAS exome AF: 0.0996

Gnomad4 SAS exome AF: 0.168

Gnomad4 FIN exome AF: 0.0699

Gnomad4 NFE exome AF: 0.0731

Gnomad4 OTH exome AF: 0.104

GnomAD4 genome AF: 0.0850 AC: 9514 AN: 111875 Hom.: 445 Cov.: 23 AF XY: 0.0854 AC XY: 2910 AN XY: 34073

Gnomad4 AFR AF: 0.0558

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.0547

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.0658

Gnomad4 NFE AF: 0.0702

Gnomad4 OTH AF: 0.119

Alfa AF: 0.0768 Hom.: 487

Bravo AF: 0.0995

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.3
DANN	Benign	0.77

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: rs3859991; hg19: chrX-130222535;