NM_021226.4:c.867-197T>C

Variant names:

• chr10-48453622-A-G
• rs4838592
• NM_021226.4:c.867-197T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021226.4(ARHGAP22):​c.867-197T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.848 in 152,214 control chromosomes in the GnomAD database, including 56,526 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 0.85 (56526 hom., cov: 34)
• Consequence: ARHGAP22 NM_021226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.508
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021226.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP22	NM_021226.4	MANE Select	c.867-197T>C		intron	N/A	NP_067049.2
	ARHGAP22	NM_001256024.2		c.915-197T>C		intron	N/A	NP_001242953.1	Q7Z5H3-2
	ARHGAP22	NM_001256025.3		c.885-197T>C		intron	N/A	NP_001242954.1	Q7Z5H3-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP22	ENST00000249601.9	TSL:1 MANE Select	c.867-197T>C		intron	N/A	ENSP00000249601.4	Q7Z5H3-1
	ARHGAP22	ENST00000417912.6	TSL:1	c.915-197T>C		intron	N/A	ENSP00000412461.2	Q7Z5H3-2
	ARHGAP22	ENST00000435790.6	TSL:2	c.885-197T>C		intron	N/A	ENSP00000416701.2	Q7Z5H3-5

Frequencies

GnomAD3 genomes AF: 0.848 AC: 128983 AN: 152098 Hom.: 56510 Cov.: 34

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.959

Gnomad AMR AF: 0.918

Gnomad ASJ AF: 0.907

Gnomad EAS AF: 0.974

Gnomad SAS AF: 0.840

Gnomad FIN AF: 0.966

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.946

Gnomad OTH AF: 0.866

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

GnomAD4 genome AF: 0.848 AC: 129038 AN: 152214 Hom.: 56526 Cov.: 34 AF XY: 0.853 AC XY: 63468 AN XY: 74432

African (AFR) AF: 0.606 AC: 25145 AN: 41492

American (AMR) AF: 0.919 AC: 14055 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.907 AC: 3149 AN: 3472

East Asian (EAS) AF: 0.974 AC: 5036 AN: 5172

South Asian (SAS) AF: 0.842 AC: 4062 AN: 4824

European-Finnish (FIN) AF: 0.966 AC: 10251 AN: 10616

Middle Eastern (MID) AF: 0.942 AC: 277 AN: 294

European-Non Finnish (NFE) AF: 0.946 AC: 64364 AN: 68020

Other (OTH) AF: 0.864 AC: 1824 AN: 2112

Alfa AF: 0.913 Hom.: 77758

Bravo AF: 0.836

Asia WGS AF: 0.880 AC: 3061 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	9.4
DANN	Benign	0.82
PhyloP100		0.51
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs4838592; hg19: chr10-49661665;