chr1-161047766-C-T

Variant names:

• chr1-161047766-C-T
• rs2774279
• NM_001025598.2:c.3255G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001025598.2(ARHGAP30):​c.3255G>A​(p.Arg1085Arg) 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
• Publications: 43 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001025598.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP30	NM_001025598.2	MANE Select	c.3255G>A	p.Arg1085Arg	synonymous	Exon 12 of 12	NP_001020769.1
	ARHGAP30	NM_001287600.2		c.2811G>A	p.Arg937Arg	synonymous	Exon 11 of 11	NP_001274529.1
	ARHGAP30	NM_001287602.2		c.2724G>A	p.Arg908Arg	synonymous	Exon 8 of 8	NP_001274531.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP30	ENST00000368013.8	TSL:2 MANE Select	c.3255G>A	p.Arg1085Arg	synonymous	Exon 12 of 12	ENSP00000356992.3
	ARHGAP30	ENST00000368015.1	TSL:5	c.2724G>A	p.Arg908Arg	synonymous	Exon 8 of 8	ENSP00000356994.1
	ARHGAP30	ENST00000368016.7	TSL:5	c.2622G>A	p.Arg874Arg	synonymous	Exon 13 of 13	ENSP00000356995.3

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

GnomAD2 exomes AF: 0.268 AC: 55625 AN: 207904 AF XY: 0.276

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 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

African (AFR) AF: 0.178 AC: 5608 AN: 31546

American (AMR) AF: 0.169 AC: 6044 AN: 35756

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 6071 AN: 22192

East Asian (EAS) AF: 0.128 AC: 5032 AN: 39438

South Asian (SAS) AF: 0.295 AC: 22840 AN: 77480

European-Finnish (FIN) AF: 0.258 AC: 13311 AN: 51610

Middle Eastern (MID) AF: 0.285 AC: 1566 AN: 5488

European-Non Finnish (NFE) AF: 0.342 AC: 373803 AN: 1091504

Other (OTH) AF: 0.298 AC: 17348 AN: 58244

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

African (AFR) AF: 0.191 AC: 7923 AN: 41444

American (AMR) AF: 0.225 AC: 3431 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 957 AN: 3468

East Asian (EAS) AF: 0.145 AC: 750 AN: 5164

South Asian (SAS) AF: 0.300 AC: 1447 AN: 4820

European-Finnish (FIN) AF: 0.273 AC: 2886 AN: 10560

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.335 AC: 22766 AN: 67954

Other (OTH) AF: 0.280 AC: 590 AN: 2110

Alfa AF: 0.309 Hom.: 14275

Bravo AF: 0.263

Asia WGS AF: 0.207 AC: 716 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.69
DANN	Benign	0.73
PhyloP100		-0.73
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2774279; hg19: chr1-161017556; COSMIC: COSV63518811; COSMIC: COSV63518811;