NM_021226.4:c.323-18832C>T

Variant names:

• chr10-48498596-G-A
• rs7898936
• NM_021226.4:c.323-18832C>T

Variant summary

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

The NM_021226.4(ARHGAP22):​c.323-18832C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 152,010 control chromosomes in the GnomAD database, including 7,265 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 0.23 (7265 hom., cov: 32)
• Consequence: ARHGAP22 NM_021226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 0 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP22	NM_021226.4	c.323-18832C>T		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.323-18832C>T		intron_variant	Intron 3 of 9	1	NM_021226.4	ENSP00000249601.4

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35574 AN: 151892 Hom.: 7255 Cov.: 32

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0870

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.234 AC: 35634 AN: 152010 Hom.: 7265 Cov.: 32 AF XY: 0.233 AC XY: 17347 AN XY: 74312

African (AFR) AF: 0.523 AC: 21650 AN: 41428

American (AMR) AF: 0.141 AC: 2150 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 472 AN: 3472

East Asian (EAS) AF: 0.589 AC: 3022 AN: 5134

South Asian (SAS) AF: 0.167 AC: 803 AN: 4810

European-Finnish (FIN) AF: 0.108 AC: 1140 AN: 10574

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.0870 AC: 5918 AN: 67996

Other (OTH) AF: 0.187 AC: 394 AN: 2112

Alfa AF: 0.0557 Hom.: 62

Bravo AF: 0.251

Asia WGS AF: 0.353 AC: 1226 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	0.80
DANN	Benign	0.86
PhyloP100		-1.1
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: rs7898936; hg19: chr10-49706639;