10-48586565-T-C

Variant names:

• chr10-48586565-T-C
• rs1965169
• NM_021226.4:c.35-3413A>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.35-3413A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 152,174 control chromosomes in the GnomAD database, including 49,245 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 0.80 (49245 hom., cov: 32)
• Consequence: ARHGAP22 NM_021226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.657
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP22	NM_021226.4	c.35-3413A>G		intron_variant	Intron 1 of 9	ENST00000249601.9	NP_067049.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP22	ENST00000249601.9	c.35-3413A>G		intron_variant	Intron 1 of 9	1	NM_021226.4	ENSP00000249601.4

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121851 AN: 152056 Hom.: 49226 Cov.: 32

Gnomad AFR AF: 0.706

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.838

Gnomad ASJ AF: 0.781

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.930

Gnomad FIN AF: 0.871

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.819

Gnomad OTH AF: 0.772

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

GnomAD4 genome AF: 0.801 AC: 121913 AN: 152174 Hom.: 49245 Cov.: 32 AF XY: 0.807 AC XY: 60061 AN XY: 74422

African (AFR) AF: 0.705 AC: 29226 AN: 41464

American (AMR) AF: 0.838 AC: 12825 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.781 AC: 2711 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5179 AN: 5186

South Asian (SAS) AF: 0.930 AC: 4483 AN: 4822

European-Finnish (FIN) AF: 0.871 AC: 9245 AN: 10612

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.819 AC: 55696 AN: 68002

Other (OTH) AF: 0.774 AC: 1637 AN: 2114

Alfa AF: 0.772 Hom.: 3015

Bravo AF: 0.789

Asia WGS AF: 0.945 AC: 3287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.8
DANN	Benign	0.71
PhyloP100		-0.66
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: rs1965169; hg19: chr10-49794610;