rs3789320

Variant names:

• chr10-48447320-C-A
• rs3789320
• NM_021226.4:c.1869-701G>T

Variant summary

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

The NM_021226.4(ARHGAP22):​c.1869-701G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 152,020 control chromosomes in the GnomAD database, including 20,181 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 0.51 (20181 hom., cov: 33)
• Consequence: ARHGAP22 NM_021226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.169
• Publications: 1 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 = 0.619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP22	NM_021226.4	c.1869-701G>T		intron_variant	Intron 9 of 9	ENST00000249601.9	NP_067049.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP22	ENST00000249601.9	c.1869-701G>T		intron_variant	Intron 9 of 9	1	NM_021226.4	ENSP00000249601.4

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76853 AN: 151902 Hom.: 20176 Cov.: 33

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.637

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.534

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

GnomAD4 genome AF: 0.506 AC: 76876 AN: 152020 Hom.: 20181 Cov.: 33 AF XY: 0.506 AC XY: 37575 AN XY: 74320

African (AFR) AF: 0.367 AC: 15208 AN: 41446

American (AMR) AF: 0.488 AC: 7463 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 2036 AN: 3470

East Asian (EAS) AF: 0.637 AC: 3296 AN: 5174

South Asian (SAS) AF: 0.412 AC: 1983 AN: 4810

European-Finnish (FIN) AF: 0.553 AC: 5839 AN: 10556

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.577 AC: 39191 AN: 67962

Other (OTH) AF: 0.527 AC: 1113 AN: 2110

Alfa AF: 0.524 Hom.: 2759

Bravo AF: 0.502

Asia WGS AF: 0.496 AC: 1726 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.0
DANN	Benign	0.77
PhyloP100		0.17
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: rs3789320; hg19: chr10-49655363;