rs3813864

chr10-48451800-G-Achr10-48451800-G-C

Variant summary

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

The NM_021226.4(ARHGAP22):c.989-660C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 139,148 control chromosomes in the GnomAD database, including 2,569 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 0.18 (2569 hom., cov: 25)
• Consequence: ARHGAP22 NM_021226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.907

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP22	NM_021226.4	c.989-660C>T		intron_variant		ENST00000249601.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP22	ENST00000249601.9	c.989-660C>T		intron_variant		1	NM_021226.4	P4

Frequencies

GnomAD3 genomes AF: 0.182 AC: 25346 AN: 139028 Hom.: 2565 Cov.: 25

Gnomad AFR AF: 0.0708

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.0709

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.182 AC: 25346 AN: 139148 Hom.: 2569 Cov.: 25 AF XY: 0.186 AC XY: 12542 AN XY: 67374

Gnomad4 AFR AF: 0.0706

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.172

Alfa AF: 0.207 Hom.: 3882

Bravo AF: 0.154

Asia WGS AF: 0.266 AC: 922 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	3.1
Dann	Benign	0.66

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: rs3813864; hg19: chr10-49659843;