rs1051509

Positions:

• chr10-48446152-A-G
• chr10-48446152-A-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ARHGAP22 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ARHGAP22	NM_021226.4	c.*239T>C		3_prime_UTR_variant	10/10	ENST00000249601.9	NP_067049.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP22	ENST00000249601.9	c.*239T>C		3_prime_UTR_variant	10/10	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

Gnomad4 AFR exome AF: 0.270

Gnomad4 AMR exome AF: 0.468

Gnomad4 ASJ exome AF: 0.361

Gnomad4 EAS exome AF: 0.350

Gnomad4 SAS exome AF: 0.550

Gnomad4 FIN exome AF: 0.473

Gnomad4 NFE exome AF: 0.420

Gnomad4 OTH exome AF: 0.408

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

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.467

Gnomad4 ASJ AF: 0.358

Gnomad4 EAS AF: 0.360

Gnomad4 SAS AF: 0.560

Gnomad4 FIN AF: 0.448

Gnomad4 NFE AF: 0.419

Gnomad4 OTH AF: 0.383

Alfa AF: 0.410 Hom.: 11954

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1051509; hg19: chr10-49654195;