rs2774279

Positions:

• chr1-161047766-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001025598.2(ARHGAP30):​c.3255G>A​(p.Arg1085=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 1,565,260 control chromosomes in the GnomAD database, including 80,395 homozygotes. 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 0.27 (5877 hom., cov: 32)
  • Exomes 𝑓: 0.32 (74518 hom.)
• Consequence: ARHGAP30 NM_001025598.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.732

Genes affected

ARHGAP30 (HGNC:27414): (Rho GTPase activating protein 30) Predicted to enable GTPase activator activity. Predicted to be involved in small GTPase mediated signal transduction. Located in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP7: Synonymous conserved (PhyloP=-0.732 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP30	NM_001025598.2	c.3255G>A	p.Arg1085=	synonymous_variant	12/12	ENST00000368013.8	NP_001020769.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP30	ENST00000368013.8	c.3255G>A	p.Arg1085=	synonymous_variant	12/12	2	NM_001025598.2	ENSP00000356992	P2
ARHGAP30	ENST00000368015.1	c.2724G>A	p.Arg908=	synonymous_variant	8/8	5		ENSP00000356994
ARHGAP30	ENST00000368016.7	c.2622G>A	p.Arg874=	synonymous_variant	13/13	5		ENSP00000356995	A2
ARHGAP30	ENST00000461003.5	n.4037G>A		non_coding_transcript_exon_variant	10/10	2

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41101 AN: 151884 Hom.: 5873 Cov.: 32

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.276

GnomAD3 exomes AF: 0.268 AC: 55625 AN: 207904 Hom.: 8061 AF XY: 0.276 AC XY: 30647 AN XY: 111110

Gnomad AFR exome AF: 0.181

Gnomad AMR exome AF: 0.162

Gnomad ASJ exome AF: 0.262

Gnomad EAS exome AF: 0.148

Gnomad SAS exome AF: 0.290

Gnomad FIN exome AF: 0.256

Gnomad NFE exome AF: 0.329

Gnomad OTH exome AF: 0.276

GnomAD4 exome AF: 0.320 AC: 451623 AN: 1413258 Hom.: 74518 Cov.: 36 AF XY: 0.319 AC XY: 222911 AN XY: 699732

Gnomad4 AFR exome AF: 0.178

Gnomad4 AMR exome AF: 0.169

Gnomad4 ASJ exome AF: 0.274

Gnomad4 EAS exome AF: 0.128

Gnomad4 SAS exome AF: 0.295

Gnomad4 FIN exome AF: 0.258

Gnomad4 NFE exome AF: 0.342

Gnomad4 OTH exome AF: 0.298

GnomAD4 genome AF: 0.271 AC: 41124 AN: 152002 Hom.: 5877 Cov.: 32 AF XY: 0.267 AC XY: 19860 AN XY: 74268

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.145

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.273

Gnomad4 NFE AF: 0.335

Gnomad4 OTH AF: 0.280

Alfa AF: 0.313 Hom.: 12088

Bravo AF: 0.263

Asia WGS AF: 0.207 AC: 716 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.69
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2774279; hg19: chr1-161017556; COSMIC: COSV63518811; COSMIC: COSV63518811;