10-48614756-A-G

Variant names:

• chr10-48614756-A-G
• rs3844492
• NM_001256025.3:c.53-31604T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256025.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP22	NM_001256025.3		c.53-31604T>C		intron	N/A	NP_001242954.1
	ARHGAP22	NM_001347738.2		c.53-31604T>C		intron	N/A	NP_001334667.1
	ARHGAP22	NM_001347736.2		c.53-31604T>C		intron	N/A	NP_001334665.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP22	ENST00000435790.6	TSL:2	c.53-31604T>C		intron	N/A	ENSP00000416701.2
	ARHGAP22	ENST00000460425.1	TSL:2	n.53-31604T>C		intron	N/A	ENSP00000422663.1
	ARHGAP22	ENST00000464445.1	TSL:3	n.89-31604T>C		intron	N/A

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

African (AFR) AF: 0.549 AC: 22766 AN: 41444

American (AMR) AF: 0.390 AC: 5967 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1020 AN: 3468

East Asian (EAS) AF: 0.253 AC: 1307 AN: 5172

South Asian (SAS) AF: 0.289 AC: 1394 AN: 4816

European-Finnish (FIN) AF: 0.294 AC: 3107 AN: 10558

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.296 AC: 20104 AN: 67958

Other (OTH) AF: 0.368 AC: 777 AN: 2110

Alfa AF: 0.329 Hom.: 27805

Bravo AF: 0.394

Asia WGS AF: 0.330 AC: 1148 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.4
DANN	Benign	0.42
PhyloP100		-0.96
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: rs3844492; hg19: chr10-49822801;