rs6070809

Variant names:

• chr20-38628947-C-G
• rs6070809
• ENST00000373345.9:c.579C>G

Your query was ambiguous. Multiple possible variants found:

• chr20-38628947-C-G
• chr20-38628947-C-T

Variant summary

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

The NM_001164431.3(ARHGAP40):​c.579C>G​(p.Gly193Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 1,301,856 control chromosomes in the GnomAD database, including 64,365 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. Synonymous variant affecting the same amino acid position (i.e. G193G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.35 (10104 hom., cov: 32)
  • Exomes 𝑓: 0.30 (54261 hom.)
• Consequence: ARHGAP40 NM_001164431.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81

Genes affected

ARHGAP40 (HGNC:16226): (Rho GTPase activating protein 40) Predicted to enable GTPase activator activity. Predicted to be involved in regulation of actin filament polymerization and regulation of small GTPase mediated signal transduction. Predicted to be located in cytosol. Predicted to be active in cytoplasm. [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=-0.87).
• BP7: Synonymous conserved (PhyloP=-1.82 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP40	NM_001164431.3	c.579C>G	p.Gly193Gly	synonymous_variant	Exon 4 of 15		NP_001157903.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP40	ENST00000373345.9	c.579C>G	p.Gly193Gly	synonymous_variant	Exon 4 of 15	5		ENSP00000362442.5
ARHGAP40	ENST00000243967.8	c.240C>G	p.Gly80Gly	synonymous_variant	Exon 2 of 14	5		ENSP00000243967.4

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52918 AN: 151880 Hom.: 10069 Cov.: 32

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.197

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.328

GnomAD3 exomes AF: 0.279 AC: 43240 AN: 154852 Hom.: 6545 AF XY: 0.279 AC XY: 22911 AN XY: 82102

Gnomad AFR exome AF: 0.516

Gnomad AMR exome AF: 0.227

Gnomad ASJ exome AF: 0.244

Gnomad EAS exome AF: 0.121

Gnomad SAS exome AF: 0.274

Gnomad FIN exome AF: 0.286

Gnomad NFE exome AF: 0.303

Gnomad OTH exome AF: 0.282

GnomAD4 exome AF: 0.305 AC: 350162 AN: 1149858 Hom.: 54261 Cov.: 31 AF XY: 0.303 AC XY: 170887 AN XY: 563876

Gnomad4 AFR exome AF: 0.511

Gnomad4 AMR exome AF: 0.228

Gnomad4 ASJ exome AF: 0.245

Gnomad4 EAS exome AF: 0.131

Gnomad4 SAS exome AF: 0.277

Gnomad4 FIN exome AF: 0.285

Gnomad4 NFE exome AF: 0.309

Gnomad4 OTH exome AF: 0.294

GnomAD4 genome AF: 0.349 AC: 53006 AN: 151998 Hom.: 10104 Cov.: 32 AF XY: 0.346 AC XY: 25711 AN XY: 74302

Gnomad4 AFR AF: 0.510

Gnomad4 AMR AF: 0.290

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.126

Gnomad4 SAS AF: 0.260

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.303

Gnomad4 OTH AF: 0.329

Alfa AF: 0.162 Hom.: 1066

Bravo AF: 0.355

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.17
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs6070809; hg19: chr20-37257590; COSMIC: COSV99717423;