10-48491914-C-T

Variant names:

• chr10-48491914-C-T
• rs4838605
• NM_021226.4:c.323-12150G>A

Variant summary

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

The NM_021226.4(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 NM_021226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310
• Publications: 31 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ARHGAP22	NM_021226.4	c.323-12150G>A		intron_variant	Intron 3 of 9	ENST00000249601.9	NP_067049.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP22	ENST00000249601.9	c.323-12150G>A		intron_variant	Intron 3 of 9	1	NM_021226.4	ENSP00000249601.4

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

African (AFR) AF: 0.366 AC: 15211 AN: 41510

American (AMR) AF: 0.338 AC: 5168 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 907 AN: 3472

East Asian (EAS) AF: 0.903 AC: 4672 AN: 5174

South Asian (SAS) AF: 0.519 AC: 2508 AN: 4828

European-Finnish (FIN) AF: 0.377 AC: 3997 AN: 10598

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.362 AC: 24611 AN: 67996

Other (OTH) AF: 0.360 AC: 760 AN: 2114

Alfa AF: 0.373 Hom.: 46619

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
PhyloP100		-0.031
Mutation Taster		=100/0	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: rs4838605; hg19: chr10-49699957;