10-48527518-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021226.4(ARHGAP22):c.322+27945G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 151,400 control chromosomes in the GnomAD database, including 17,566 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 0.47 (17566 hom., cov: 30)
• Consequence: ARHGAP22 NM_021226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.686

Genes affected

ARHGAP22 (HGNC:30320): (Rho GTPase activating protein 22) This gene encodes a member of the GTPase activating protein family which activates a GTPase belonging to the RAS superfamily of small GTP-binding proteins. The encoded protein is insulin-responsive, is dependent on the kinase Akt and requires the Akt-dependent 14-3-3 binding protein which binds sequentially to two serine residues. The result of these interactions is regulation of cell motility. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP22	NM_021226.4	c.322+27945G>A		intron_variant		ENST00000249601.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP22	ENST00000249601.9	c.322+27945G>A		intron_variant		1	NM_021226.4	P4

Frequencies

GnomAD3 genomes AF: 0.474 AC: 71748 AN: 151282 Hom.: 17548 Cov.: 30

Gnomad AFR AF: 0.601

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.441

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.474 AC: 71804 AN: 151400 Hom.: 17566 Cov.: 30 AF XY: 0.473 AC XY: 34949 AN XY: 73948

Gnomad4 AFR AF: 0.601

Gnomad4 AMR AF: 0.392

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.406

Gnomad4 SAS AF: 0.461

Gnomad4 FIN AF: 0.455

Gnomad4 NFE AF: 0.434

Gnomad4 OTH AF: 0.447

Alfa AF: 0.429 Hom.: 31473

Bravo AF: 0.470

Asia WGS AF: 0.465 AC: 1616 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.24
Dann	Benign	0.29

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

Publications

LitVar

Other links and lift over

dbSNP: rs10776612; hg19: chr10-49735563; COSMIC: COSV50960946; COSMIC: COSV50960946;