rs1051509

Variant names:

• chr10-48446152-A-G
• rs1051509
• NM_021226.4:c.*239T>C

Your query was ambiguous. Multiple possible variants found:

• chr10-48446152-A-G
• chr10-48446152-A-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.*239T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 556,316 control chromosomes in the GnomAD database, including 49,328 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 0.39 (11711 hom., cov: 32)
  • Exomes 𝑓: 0.42 (37617 hom.)
• Consequence: ARHGAP22 NM_021226.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.368
• Publications: 13 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP22	NM_021226.4	c.*239T>C		3_prime_UTR_variant	Exon 10 of 10	ENST00000249601.9	NP_067049.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP22	ENST00000249601.9	c.*239T>C		3_prime_UTR_variant	Exon 10 of 10	1	NM_021226.4	ENSP00000249601.4

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58428 AN: 151682 Hom.: 11705 Cov.: 32

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.562

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.376

GnomAD4 exome AF: 0.425 AC: 171765 AN: 404516 Hom.: 37617 Cov.: 3 AF XY: 0.430 AC XY: 90874 AN XY: 211168

African (AFR) AF: 0.270 AC: 3193 AN: 11820

American (AMR) AF: 0.468 AC: 7092 AN: 15166

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 4606 AN: 12762

East Asian (EAS) AF: 0.350 AC: 10116 AN: 28916

South Asian (SAS) AF: 0.550 AC: 19474 AN: 35400

European-Finnish (FIN) AF: 0.473 AC: 12775 AN: 27028

Middle Eastern (MID) AF: 0.338 AC: 621 AN: 1840

European-Non Finnish (NFE) AF: 0.420 AC: 104161 AN: 247750

Other (OTH) AF: 0.408 AC: 9727 AN: 23834

GnomAD4 genome AF: 0.385 AC: 58455 AN: 151800 Hom.: 11711 Cov.: 32 AF XY: 0.391 AC XY: 29005 AN XY: 74198

African (AFR) AF: 0.269 AC: 11116 AN: 41366

American (AMR) AF: 0.467 AC: 7135 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 1241 AN: 3470

East Asian (EAS) AF: 0.360 AC: 1857 AN: 5158

South Asian (SAS) AF: 0.560 AC: 2682 AN: 4788

European-Finnish (FIN) AF: 0.448 AC: 4732 AN: 10560

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.419 AC: 28436 AN: 67866

Other (OTH) AF: 0.383 AC: 809 AN: 2110

Alfa AF: 0.404 Hom.: 15113

Bravo AF: 0.375

Asia WGS AF: 0.469 AC: 1630 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.60
PhyloP100		-0.37
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: rs1051509; hg19: chr10-49654195;