10-48656239-C-G

Variant names:

• chr10-48656239-C-G
• rs77568722
• NM_001347738.2:c.-326G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001347738.2(ARHGAP22):​c.-326G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00171 in 142,960 control chromosomes in the GnomAD database, including 1 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 0.0017 (1 hom., cov: 29)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARHGAP22 NM_001347738.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001347738.2. 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_001347738.2		c.-326G>C		5_prime_UTR	Exon 1 of 11	NP_001334667.1	Q7Z5H3-5
	ARHGAP22	NM_001347736.2		c.-326G>C		5_prime_UTR	Exon 1 of 4	NP_001334665.1
	ARHGAP22	NR_045675.2		n.27G>C		non_coding_transcript_exon	Exon 1 of 11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP22	ENST00000460425.1	TSL:2	n.-842G>C		non_coding_transcript_exon	Exon 1 of 11	ENSP00000422663.1	D6RBJ8
	ARHGAP22	ENST00000460425.1	TSL:2	n.-842G>C		5_prime_UTR	Exon 1 of 11	ENSP00000422663.1	D6RBJ8

Frequencies

GnomAD3 genomes AF: 0.00171 AC: 244 AN: 142886 Hom.: 1 Cov.: 29

Gnomad AFR AF: 0.000197

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00119

Gnomad ASJ AF: 0.00933

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00110

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00268

Gnomad OTH AF: 0.00153

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 116 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 100

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 104

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.00171 AC: 244 AN: 142960 Hom.: 1 Cov.: 29 AF XY: 0.00175 AC XY: 122 AN XY: 69616

African (AFR) AF: 0.000196 AC: 7 AN: 35684

American (AMR) AF: 0.00118 AC: 17 AN: 14364

Ashkenazi Jewish (ASJ) AF: 0.00933 AC: 32 AN: 3430

East Asian (EAS) AF: 0.00 AC: 0 AN: 4810

South Asian (SAS) AF: 0.00111 AC: 5 AN: 4524

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9886

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 276

European-Non Finnish (NFE) AF: 0.00268 AC: 180 AN: 67098

Other (OTH) AF: 0.00151 AC: 3 AN: 1982

Alfa AF: 0.000241 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	2.6
DANN	Benign	0.80
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs77568722; hg19: chr10-49864284;