10-48553358-T-C

Variant names:

• chr10-48553358-T-C
• rs749377
• NM_021226.4:c.322+2105A>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+2105A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 152,214 control chromosomes in the GnomAD database, including 8,297 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 0.30 (8297 hom., cov: 34)
• Consequence: ARHGAP22 NM_021226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.195
• Publications: 3 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.869 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP22	NM_021226.4	MANE Select	c.322+2105A>G		intron	N/A	NP_067049.2
	ARHGAP22	NM_001256024.2		c.322+2105A>G		intron	N/A	NP_001242953.1	Q7Z5H3-2
	ARHGAP22	NM_001256025.3		c.340+2105A>G		intron	N/A	NP_001242954.1	Q7Z5H3-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP22	ENST00000249601.9	TSL:1 MANE Select	c.322+2105A>G		intron	N/A	ENSP00000249601.4	Q7Z5H3-1
	ARHGAP22	ENST00000417912.6	TSL:1	c.322+2105A>G		intron	N/A	ENSP00000412461.2	Q7Z5H3-2
	ARHGAP22	ENST00000435790.6	TSL:2	c.340+2105A>G		intron	N/A	ENSP00000416701.2	Q7Z5H3-5

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45940 AN: 152096 Hom.: 8294 Cov.: 34

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.890

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.302 AC: 45964 AN: 152214 Hom.: 8297 Cov.: 34 AF XY: 0.308 AC XY: 22908 AN XY: 74438

African (AFR) AF: 0.302 AC: 12563 AN: 41532

American (AMR) AF: 0.250 AC: 3826 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 855 AN: 3472

East Asian (EAS) AF: 0.891 AC: 4613 AN: 5180

South Asian (SAS) AF: 0.601 AC: 2901 AN: 4828

European-Finnish (FIN) AF: 0.256 AC: 2717 AN: 10602

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17680 AN: 67988

Other (OTH) AF: 0.293 AC: 618 AN: 2106

Alfa AF: 0.280 Hom.: 25550

Bravo AF: 0.297

Asia WGS AF: 0.706 AC: 2450 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.4
DANN	Benign	0.78
PhyloP100		0.20
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: rs749377; hg19: chr10-49761403;