chr12-14950705-T-A

Variant names:

• chr12-14950705-T-A
• rs764587718
• NM_001175.7:c.8A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001175.7(ARHGDIB):​c.8A>T​(p.Glu3Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,186 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E3G) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: ARHGDIB NM_001175.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.28
• Publications: 0 publications found

Genes affected

ARHGDIB (HGNC:679): (Rho GDP dissociation inhibitor beta) Members of the Rho (or ARH) protein family (see MIM 165390) and other Ras-related small GTP-binding proteins (see MIM 179520) are involved in diverse cellular events, including cell signaling, proliferation, cytoskeletal organization, and secretion. The GTP-binding proteins are active only in the GTP-bound state. At least 3 classes of proteins tightly regulate cycling between the GTP-bound and GDP-bound states: GTPase-activating proteins (GAPs), guanine nucleotide-releasing factors (GRFs), and GDP-dissociation inhibitors (GDIs). The GDIs, including ARHGDIB, decrease the rate of GDP dissociation from Ras-like GTPases (summary by Scherle et al., 1993 [PubMed 8356058]).[supplied by OMIM, Dec 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001175.7. 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
	ARHGDIB	NM_001175.7	MANE Select	c.8A>T	p.Glu3Val	missense	Exon 2 of 6	NP_001166.3	P52566
	ARHGDIB	NM_001321420.2		c.8A>T	p.Glu3Val	missense	Exon 3 of 7	NP_001308349.1	P52566
	ARHGDIB	NM_001321421.2		c.8A>T	p.Glu3Val	missense	Exon 2 of 6	NP_001308350.1	P52566

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGDIB	ENST00000228945.9	TSL:1 MANE Select	c.8A>T	p.Glu3Val	missense	Exon 2 of 6	ENSP00000228945.4	P52566
	ARHGDIB	ENST00000541546.5	TSL:5	c.8A>T	p.Glu3Val	missense	Exon 3 of 7	ENSP00000440560.1	P52566
	ARHGDIB	ENST00000541644.5	TSL:5	c.8A>T	p.Glu3Val	missense	Exon 2 of 6	ENSP00000444860.1	P52566

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152186 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152186 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74350

African (AFR) AF: 0.00 AC: 0 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000192 AC: 1 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.55	D
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		5.3
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.31
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.97	D
Vest4		0.60
MutPred		0.55		Loss of solvent accessibility (P = 0.0022)
MVP		0.65
MPC		0.55
ClinPred		0.98	D
GERP RS		5.2
PromoterAI		0.0068	Neutral
Varity_R		0.35
gMVP		0.47
Mutation Taster		=47/53	disease causing

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: rs764587718; hg19: chr12-15103639;