chr20-38628947-C-G

Variant names:

• chr20-38628947-C-G
• rs6070809
• NM_001164431.3:c.579C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.005).
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164431.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP40	NM_001164431.3	MANE Select	c.579C>G	p.Gly193Gly	synonymous	Exon 4 of 15	NP_001157903.2	Q5TG30

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP40	ENST00000373345.9	TSL:5 MANE Select	c.579C>G	p.Gly193Gly	synonymous	Exon 4 of 15	ENSP00000362442.5	Q5TG30
	ARHGAP40	ENST00000243967.8	TSL:5	c.240C>G	p.Gly80Gly	synonymous	Exon 2 of 14	ENSP00000243967.4	H7BXE0
	ARHGAP40	ENST00000906550.1		c.558+1732C>G		intron	N/A	ENSP00000576609.1

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

GnomAD2 exomes AF: 0.279 AC: 43240 AN: 154852 AF XY: 0.279

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 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

African (AFR) AF: 0.511 AC: 12376 AN: 24204

American (AMR) AF: 0.228 AC: 6385 AN: 28038

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 3895 AN: 15872

East Asian (EAS) AF: 0.131 AC: 1672 AN: 12772

South Asian (SAS) AF: 0.277 AC: 21023 AN: 75962

European-Finnish (FIN) AF: 0.285 AC: 8083 AN: 28410

Middle Eastern (MID) AF: 0.215 AC: 943 AN: 4388

European-Non Finnish (NFE) AF: 0.309 AC: 283573 AN: 918708

Other (OTH) AF: 0.294 AC: 12212 AN: 41504

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

African (AFR) AF: 0.510 AC: 21154 AN: 41446

American (AMR) AF: 0.290 AC: 4438 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 871 AN: 3468

East Asian (EAS) AF: 0.126 AC: 653 AN: 5174

South Asian (SAS) AF: 0.260 AC: 1256 AN: 4824

European-Finnish (FIN) AF: 0.278 AC: 2934 AN: 10562

Middle Eastern (MID) AF: 0.199 AC: 58 AN: 292

European-Non Finnish (NFE) AF: 0.303 AC: 20608 AN: 67918

Other (OTH) AF: 0.329 AC: 695 AN: 2110

Alfa AF: 0.162 Hom.: 1066

Bravo AF: 0.355

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.17
DANN	Benign	0.66
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6070809; hg19: chr20-37257590; COSMIC: COSV99717423;