10-48491914-C-T

Position:

• chr10-48491914-C-T

Variant summary

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

The ENST00000249601.9(ARHGAP22):​c.323-12150G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 152,194 control chromosomes in the GnomAD database, including 12,002 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 0.38 (12002 hom., cov: 33)
• Consequence: ARHGAP22 ENST00000249601.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP22	NM_021226.4	c.323-12150G>A		intron_variant		ENST00000249601.9	NP_067049.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP22	ENST00000249601.9	c.323-12150G>A		intron_variant		1	NM_021226.4	ENSP00000249601	P4

Frequencies

GnomAD3 genomes AF: 0.382 AC: 58127 AN: 152076 Hom.: 11990 Cov.: 33

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.903

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.353

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

GnomAD4 genome AF: 0.382 AC: 58169 AN: 152194 Hom.: 12002 Cov.: 33 AF XY: 0.388 AC XY: 28864 AN XY: 74414

Gnomad4 AFR AF: 0.366

Gnomad4 AMR AF: 0.338

Gnomad4 ASJ AF: 0.261

Gnomad4 EAS AF: 0.903

Gnomad4 SAS AF: 0.519

Gnomad4 FIN AF: 0.377

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.360

Alfa AF: 0.369 Hom.: 23840

Bravo AF: 0.376

Asia WGS AF: 0.687 AC: 2385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.4
DANN	Benign	0.71

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: rs4838605; hg19: chr10-49699957;