chr10-48455141-G-A

Variant names:

• chr10-48455141-G-A
• rs72796308
• NM_021226.4:c.660-7C>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.660-7C>T variant causes a splice region, 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, intron
• Scores: Splicing: ADA: 0.00002077
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.250
• Publications: 3 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=-0.84).
• 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 rank	MANE	Protein	UniProt
ARHGAP22	NM_021226.4	c.660-7C>T		splice_region_variant, intron_variant	Intron 5 of 9	ENST00000249601.9	NP_067049.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP22	ENST00000249601.9	c.660-7C>T		splice_region_variant, intron_variant	Intron 5 of 9	1	NM_021226.4	ENSP00000249601.4

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

GnomAD2 exomes AF: 0.0970 AC: 23540 AN: 242722 AF XY: 0.0990

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 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

African (AFR) AF: 0.111 AC: 3695 AN: 33368

American (AMR) AF: 0.0468 AC: 2073 AN: 44342

Ashkenazi Jewish (ASJ) AF: 0.0830 AC: 2140 AN: 25772

East Asian (EAS) AF: 0.0512 AC: 2023 AN: 39530

South Asian (SAS) AF: 0.112 AC: 9569 AN: 85204

European-Finnish (FIN) AF: 0.137 AC: 7038 AN: 51536

Middle Eastern (MID) AF: 0.0913 AC: 489 AN: 5354

European-Non Finnish (NFE) AF: 0.110 AC: 121871 AN: 1105282

Other (OTH) AF: 0.111 AC: 6649 AN: 59870

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

African (AFR) AF: 0.116 AC: 4820 AN: 41550

American (AMR) AF: 0.0749 AC: 1146 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0971 AC: 337 AN: 3472

East Asian (EAS) AF: 0.0607 AC: 315 AN: 5188

South Asian (SAS) AF: 0.107 AC: 515 AN: 4830

European-Finnish (FIN) AF: 0.138 AC: 1462 AN: 10614

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7350 AN: 68006

Other (OTH) AF: 0.0976 AC: 206 AN: 2110

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
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs72796308; hg19: chr10-49663184; COSMIC: COSV50963829; COSMIC: COSV50963829;