10-48541529-C-T

Variant names:

• chr10-48541529-C-T
• rs1445151
• NM_021226.4:c.322+13934G>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.322+13934G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 151,994 control chromosomes in the GnomAD database, including 26,423 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 0.57 (26423 hom., cov: 32)
• Consequence: ARHGAP22 NM_021226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.780
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021226.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP22	NM_021226.4	MANE Select	c.322+13934G>A		intron	N/A	NP_067049.2
	ARHGAP22	NM_001256024.2		c.322+13934G>A		intron	N/A	NP_001242953.1
	ARHGAP22	NM_001256025.3		c.340+13934G>A		intron	N/A	NP_001242954.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP22	ENST00000249601.9	TSL:1 MANE Select	c.322+13934G>A		intron	N/A	ENSP00000249601.4
	ARHGAP22	ENST00000417912.6	TSL:1	c.322+13934G>A		intron	N/A	ENSP00000412461.2
	ARHGAP22	ENST00000435790.6	TSL:2	c.340+13934G>A		intron	N/A	ENSP00000416701.2

Frequencies

GnomAD3 genomes AF: 0.574 AC: 87130 AN: 151876 Hom.: 26396 Cov.: 32

Gnomad AFR AF: 0.704

Gnomad AMI AF: 0.415

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.986

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.516

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

GnomAD4 genome AF: 0.574 AC: 87211 AN: 151994 Hom.: 26423 Cov.: 32 AF XY: 0.577 AC XY: 42863 AN XY: 74310

African (AFR) AF: 0.704 AC: 29157 AN: 41432

American (AMR) AF: 0.442 AC: 6762 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 1547 AN: 3468

East Asian (EAS) AF: 0.987 AC: 5091 AN: 5160

South Asian (SAS) AF: 0.721 AC: 3468 AN: 4812

European-Finnish (FIN) AF: 0.538 AC: 5685 AN: 10572

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.499 AC: 33876 AN: 67946

Other (OTH) AF: 0.521 AC: 1098 AN: 2108

Alfa AF: 0.548 Hom.: 2984

Bravo AF: 0.568

Asia WGS AF: 0.833 AC: 2894 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.71
PhyloP100		-0.78
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: rs1445151; hg19: chr10-49749574;