chr10-48575452-C-T

Variant names:

• chr10-48575452-C-T
• rs7896935
• NM_021226.4:c.234+7501G>A

Variant summary

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

The NM_001347736.2(ARHGAP22):​c.*195G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0791 in 152,200 control chromosomes in the GnomAD database, including 593 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 0.079 (593 hom., cov: 33)
  • Exomes 𝑓: 0.33 (0 hom.)
• Consequence: ARHGAP22 NM_001347736.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.184
• Publications: 1 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001347736.2. 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.234+7501G>A		intron	N/A	NP_067049.2
	ARHGAP22	NM_001347736.2		c.*195G>A		3_prime_UTR	Exon 4 of 4	NP_001334665.1
	ARHGAP22	NM_001347737.2		c.*195G>A		3_prime_UTR	Exon 3 of 3	NP_001334666.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP22	ENST00000249601.9	TSL:1 MANE Select	c.234+7501G>A		intron	N/A	ENSP00000249601.4	Q7Z5H3-1
	ARHGAP22	ENST00000417912.6	TSL:1	c.234+7501G>A		intron	N/A	ENSP00000412461.2	Q7Z5H3-2
	ARHGAP22	ENST00000435790.6	TSL:2	c.252+7501G>A		intron	N/A	ENSP00000416701.2	Q7Z5H3-5

Frequencies

GnomAD3 genomes AF: 0.0791 AC: 12035 AN: 152076 Hom.: 591 Cov.: 33

Gnomad AFR AF: 0.0196

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.0988

Gnomad ASJ AF: 0.0415

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0831

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.0681

GnomAD4 exome AF: 0.333 AC: 2 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.333 AC XY: 2 AN XY: 6

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 1 AN: 4

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.0791 AC: 12035 AN: 152194 Hom.: 593 Cov.: 33 AF XY: 0.0811 AC XY: 6031 AN XY: 74408

African (AFR) AF: 0.0195 AC: 810 AN: 41528

American (AMR) AF: 0.0988 AC: 1510 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0415 AC: 144 AN: 3470

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5178

South Asian (SAS) AF: 0.0831 AC: 401 AN: 4824

European-Finnish (FIN) AF: 0.141 AC: 1492 AN: 10590

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7429 AN: 68002

Other (OTH) AF: 0.0669 AC: 141 AN: 2108

Alfa AF: 0.0858 Hom.: 71

Bravo AF: 0.0705

Asia WGS AF: 0.0400 AC: 141 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.8
DANN	Benign	0.77
PhyloP100		0.18
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: rs7896935; hg19: chr10-49783497;