chr1-161049250-G-C

Variant names:

• chr1-161049250-G-C
• rs3813609
• NM_001025598.2:c.1771C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001025598.2(ARHGAP30):​c.1771C>G​(p.Leu591Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 1,613,834 control chromosomes in the GnomAD database, including 272,464 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.49 (19956 hom., cov: 31)
  • Exomes 𝑓: 0.58 (252508 hom.)
• Consequence: ARHGAP30 NM_001025598.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47
• Publications: 38 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.745938E-6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP30	NM_001025598.2	c.1771C>G	p.Leu591Val	missense_variant	Exon 12 of 12	ENST00000368013.8	NP_001020769.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP30	ENST00000368013.8	c.1771C>G	p.Leu591Val	missense_variant	Exon 12 of 12	2	NM_001025598.2	ENSP00000356992.3

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74198 AN: 151904 Hom.: 19955 Cov.: 31

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.627

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.615

Gnomad OTH AF: 0.518

GnomAD2 exomes AF: 0.520 AC: 130138 AN: 250080 AF XY: 0.529

Gnomad AFR exome AF: 0.244

Gnomad AMR exome AF: 0.420

Gnomad ASJ exome AF: 0.572

Gnomad EAS exome AF: 0.331

Gnomad FIN exome AF: 0.616

Gnomad NFE exome AF: 0.613

Gnomad OTH exome AF: 0.551

GnomAD4 exome AF: 0.581 AC: 849247 AN: 1461810 Hom.: 252508 Cov.: 89 AF XY: 0.579 AC XY: 421105 AN XY: 727198

African (AFR) AF: 0.240 AC: 8019 AN: 33480

American (AMR) AF: 0.424 AC: 18974 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 15048 AN: 26136

East Asian (EAS) AF: 0.328 AC: 13019 AN: 39700

South Asian (SAS) AF: 0.465 AC: 40107 AN: 86258

European-Finnish (FIN) AF: 0.611 AC: 32585 AN: 53368

Middle Eastern (MID) AF: 0.543 AC: 3130 AN: 5768

European-Non Finnish (NFE) AF: 0.616 AC: 685370 AN: 1111990

Other (OTH) AF: 0.546 AC: 32995 AN: 60386

GnomAD4 genome AF: 0.488 AC: 74218 AN: 152024 Hom.: 19956 Cov.: 31 AF XY: 0.486 AC XY: 36106 AN XY: 74304

African (AFR) AF: 0.257 AC: 10652 AN: 41448

American (AMR) AF: 0.474 AC: 7237 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.588 AC: 2042 AN: 3472

East Asian (EAS) AF: 0.330 AC: 1704 AN: 5166

South Asian (SAS) AF: 0.474 AC: 2283 AN: 4816

European-Finnish (FIN) AF: 0.627 AC: 6639 AN: 10586

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.615 AC: 41780 AN: 67944

Other (OTH) AF: 0.519 AC: 1097 AN: 2114

Alfa AF: 0.575 Hom.: 8276

Bravo AF: 0.470

TwinsUK AF: 0.624 AC: 2313

ALSPAC AF: 0.604 AC: 2326

ESP6500AA AF: 0.263 AC: 1158

ESP6500EA AF: 0.607 AC: 5222

ExAC AF: 0.519 AC: 63008

Asia WGS AF: 0.353 AC: 1231 AN: 3478

EpiCase AF: 0.610

EpiControl AF: 0.613

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	6.1
DANN	Benign	0.97
DEOGEN2	Benign	0.017	.;T;.
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.55	T;T;T
MetaRNN	Benign	0.0000087	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	.;N;.
PhyloP100		1.5
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.050	N;N;N
REVEL	Benign	0.099
Sift	Benign	0.19	T;T;T
Sift4G	Benign	0.65	T;T;T
Polyphen		0.36	.;B;.
Vest4		0.064
MPC		0.056
ClinPred		0.0089	T
GERP RS		1.1
Varity_R		0.049
gMVP		0.10
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3813609; hg19: chr1-161019040; COSMIC: COSV63514856; COSMIC: COSV63514856;