rs3844492

chr10-48614756-A-G

Variant summary

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

The NM_001256025.3(ARHGAP22):c.53-31604T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 152,010 control chromosomes in the GnomAD database, including 11,564 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 0.37 (11564 hom., cov: 32)
• Consequence: ARHGAP22 NM_001256025.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.961

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP22	NM_001256025.3	c.53-31604T>C		intron_variant
ARHGAP22	NM_001347736.2	c.53-31604T>C		intron_variant
ARHGAP22	NM_001347738.2	c.53-31604T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP22	ENST00000435790.6	c.53-31604T>C		intron_variant		2		A2
ARHGAP22	ENST00000460425.1	c.53-31604T>C		intron_variant, NMD_transcript_variant		2
ARHGAP22	ENST00000464445.1	n.89-31604T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56815 AN: 151892 Hom.: 11545 Cov.: 32

Gnomad AFR AF: 0.549

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.365

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

GnomAD4 genome AF: 0.374 AC: 56887 AN: 152010 Hom.: 11564 Cov.: 32 AF XY: 0.373 AC XY: 27707 AN XY: 74316

Gnomad4 AFR AF: 0.549

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.294

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.289

Gnomad4 FIN AF: 0.294

Gnomad4 NFE AF: 0.296

Gnomad4 OTH AF: 0.368

Alfa AF: 0.313 Hom.: 15622

Bravo AF: 0.394

Asia WGS AF: 0.330 AC: 1148 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	1.4
Dann	Benign	0.42

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3844492; hg19: chr10-49822801;