chr10-48629734-T-C

Variant names:

• chr10-48629734-T-C
• rs11101409
• NM_001256025.3:c.52+22500A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001256025.3(ARHGAP22):​c.52+22500A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00717 in 152,358 control chromosomes in the GnomAD database, including 7 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 0.0072 (7 hom., cov: 32)
• Consequence: ARHGAP22 NM_001256025.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.264
• 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP22	NM_001256025.3		c.52+22500A>G		intron	N/A	NP_001242954.1	Q7Z5H3-5
	ARHGAP22	NM_001347738.2		c.52+22500A>G		intron	N/A	NP_001334667.1	Q7Z5H3-5
	ARHGAP22	NM_001347736.2		c.52+22500A>G		intron	N/A	NP_001334665.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP22	ENST00000435790.6	TSL:2	c.52+22500A>G		intron	N/A	ENSP00000416701.2	Q7Z5H3-5
	ARHGAP22	ENST00000460425.1	TSL:2	n.52+22500A>G		intron	N/A	ENSP00000422663.1	D6RBJ8
	ARHGAP22	ENST00000464445.1	TSL:3	n.88+22500A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00715 AC: 1089 AN: 152240 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00195

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.00517

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00848

Gnomad FIN AF: 0.00490

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0115

Gnomad OTH AF: 0.00764

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

GnomAD4 genome AF: 0.00717 AC: 1092 AN: 152358 Hom.: 7 Cov.: 32 AF XY: 0.00664 AC XY: 495 AN XY: 74512

African (AFR) AF: 0.00195 AC: 81 AN: 41580

American (AMR) AF: 0.00516 AC: 79 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 12 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5192

South Asian (SAS) AF: 0.00870 AC: 42 AN: 4830

European-Finnish (FIN) AF: 0.00490 AC: 52 AN: 10618

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0116 AC: 786 AN: 68034

Other (OTH) AF: 0.00756 AC: 16 AN: 2116

Alfa AF: 0.00879 Hom.: 1

Bravo AF: 0.00724

Asia WGS AF: 0.00347 AC: 14 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.8
DANN	Benign	0.76
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs11101409; hg19: chr10-49837779;