rs1822861

Variant names:

• chr10-48626281-G-T
• rs1822861
• NM_001256025.3:c.52+25953C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 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=-0.91).
• 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 rank	MANE	Protein	UniProt
ARHGAP22	NM_001256025.3	c.52+25953C>A		intron_variant	Intron 1 of 9		NP_001242954.1
ARHGAP22	NM_001347738.2	c.52+25953C>A		intron_variant	Intron 2 of 10		NP_001334667.1
ARHGAP22	NM_001347736.2	c.52+25953C>A		intron_variant	Intron 2 of 3		NP_001334665.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP22	ENST00000435790.6	c.52+25953C>A		intron_variant	Intron 1 of 9	2		ENSP00000416701.2
ARHGAP22	ENST00000460425.1	n.52+25953C>A		intron_variant	Intron 2 of 10	2		ENSP00000422663.1
ARHGAP22	ENST00000464445.1	n.88+25953C>A		intron_variant	Intron 1 of 1	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

African (AFR) AF: 0.342 AC: 14159 AN: 41406

American (AMR) AF: 0.553 AC: 8453 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1641 AN: 3468

East Asian (EAS) AF: 0.531 AC: 2740 AN: 5158

South Asian (SAS) AF: 0.514 AC: 2475 AN: 4812

European-Finnish (FIN) AF: 0.560 AC: 5902 AN: 10542

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.489 AC: 33249 AN: 67954

Other (OTH) AF: 0.470 AC: 992 AN: 2112

Alfa AF: 0.481 Hom.: 78309

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
PhyloP100		-0.22
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1822861; hg19: chr10-49834326;