10-48555121-T-C

Variant names:

• chr10-48555121-T-C
• rs10776614
• NM_021226.4:c.322+342A>G

Variant summary

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

The NM_021226.4(ARHGAP22):​c.322+342A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.829 in 152,194 control chromosomes in the GnomAD database, including 52,426 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 0.83 (52426 hom., cov: 33)
• Consequence: ARHGAP22 NM_021226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.329
• Publications: 7 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP22	NM_021226.4	c.322+342A>G		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.322+342A>G		intron_variant	Intron 3 of 9	1	NM_021226.4	ENSP00000249601.4

Frequencies

GnomAD3 genomes AF: 0.829 AC: 126118 AN: 152076 Hom.: 52389 Cov.: 33

Gnomad AFR AF: 0.837

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.759

Gnomad ASJ AF: 0.885

Gnomad EAS AF: 0.920

Gnomad SAS AF: 0.883

Gnomad FIN AF: 0.798

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.833

Gnomad OTH AF: 0.847

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

GnomAD4 genome AF: 0.829 AC: 126208 AN: 152194 Hom.: 52426 Cov.: 33 AF XY: 0.828 AC XY: 61596 AN XY: 74402

African (AFR) AF: 0.837 AC: 34728 AN: 41506

American (AMR) AF: 0.759 AC: 11610 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.885 AC: 3071 AN: 3472

East Asian (EAS) AF: 0.920 AC: 4775 AN: 5188

South Asian (SAS) AF: 0.883 AC: 4258 AN: 4824

European-Finnish (FIN) AF: 0.798 AC: 8436 AN: 10572

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.833 AC: 56662 AN: 68020

Other (OTH) AF: 0.848 AC: 1793 AN: 2114

Alfa AF: 0.832 Hom.: 79604

Bravo AF: 0.823

Asia WGS AF: 0.908 AC: 3158 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.49
PhyloP100		-0.33
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: rs10776614; hg19: chr10-49763166;