rs72796308

chr10-48455141-G-Achr10-48455141-G-Cchr10-48455141-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021226.4(ARHGAP22):c.660-7C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,602,532 control chromosomes in the GnomAD database, including 9,569 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.11 (904 hom., cov: 33)
  • Exomes 𝑓: 0.11 (8665 hom.)
• Consequence: ARHGAP22 NM_021226.4 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00002077
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.250

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP22	NM_021226.4	c.660-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000249601.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP22	ENST00000249601.9	c.660-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_021226.4	P4

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16388 AN: 152156 Hom.: 905 Cov.: 33

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.0751

Gnomad ASJ AF: 0.0971

Gnomad EAS AF: 0.0610

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.0982

GnomAD3 exomes AF: 0.0970 AC: 23540 AN: 242722 Hom.: 1238 AF XY: 0.0990 AC XY: 13045 AN XY: 131806

Gnomad AFR exome AF: 0.118

Gnomad AMR exome AF: 0.0422

Gnomad ASJ exome AF: 0.0822

Gnomad EAS exome AF: 0.0619

Gnomad SAS exome AF: 0.113

Gnomad FIN exome AF: 0.136

Gnomad NFE exome AF: 0.107

Gnomad OTH exome AF: 0.0942

GnomAD4 exome AF: 0.107 AC: 155547 AN: 1450258 Hom.: 8665 Cov.: 32 AF XY: 0.107 AC XY: 77318 AN XY: 720194

Gnomad4 AFR exome AF: 0.111

Gnomad4 AMR exome AF: 0.0468

Gnomad4 ASJ exome AF: 0.0830

Gnomad4 EAS exome AF: 0.0512

Gnomad4 SAS exome AF: 0.112

Gnomad4 FIN exome AF: 0.137

Gnomad4 NFE exome AF: 0.110

Gnomad4 OTH exome AF: 0.111

GnomAD4 genome AF: 0.108 AC: 16397 AN: 152274 Hom.: 904 Cov.: 33 AF XY: 0.109 AC XY: 8128 AN XY: 74454

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.0749

Gnomad4 ASJ AF: 0.0971

Gnomad4 EAS AF: 0.0607

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.0976

Alfa AF: 0.0623 Hom.: 90

Bravo AF: 0.104

Asia WGS AF: 0.0730 AC: 255 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.3
Dann	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000021
dbscSNV1_RF	Benign	0.0
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: rs72796308; hg19: chr10-49663184; COSMIC: COSV50963829; COSMIC: COSV50963829;