10-48626281-G-T

Position:

• chr10-48626281-G-T

Variant summary

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

The NM_001256025.3(ARHGAP22):​c.52+25953C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 151,940 control chromosomes in the GnomAD database, including 16,759 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 0.46 (16759 hom., cov: 31)
• Consequence: ARHGAP22 NM_001256025.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.222

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP22	NM_001256025.3	c.52+25953C>A		intron_variant			NP_001242954.1
ARHGAP22	NM_001347736.2	c.52+25953C>A		intron_variant			NP_001334665.1
ARHGAP22	NM_001347738.2	c.52+25953C>A		intron_variant			NP_001334667.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP22	ENST00000435790.6	c.52+25953C>A		intron_variant		2		ENSP00000416701	A2
ARHGAP22	ENST00000460425.1	c.52+25953C>A		intron_variant, NMD_transcript_variant		2		ENSP00000422663
ARHGAP22	ENST00000464445.1	n.88+25953C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70130 AN: 151822 Hom.: 16733 Cov.: 31

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.463

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

GnomAD4 genome AF: 0.462 AC: 70191 AN: 151940 Hom.: 16759 Cov.: 31 AF XY: 0.469 AC XY: 34794 AN XY: 74254

Gnomad4 AFR AF: 0.342

Gnomad4 AMR AF: 0.553

Gnomad4 ASJ AF: 0.473

Gnomad4 EAS AF: 0.531

Gnomad4 SAS AF: 0.514

Gnomad4 FIN AF: 0.560

Gnomad4 NFE AF: 0.489

Gnomad4 OTH AF: 0.470

Alfa AF: 0.488 Hom.: 37744

Bravo AF: 0.458

Asia WGS AF: 0.553 AC: 1925 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.28
DANN	Benign	0.37

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1822861; hg19: chr10-49834326;