rs12491012

Variant names:

• chr3-154249701-G-A
• rs12491012
• NM_015595.4:c.2301-3415G>A

Variant summary

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

The NM_015595.4(ARHGEF26):​c.2301-3415G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,166 control chromosomes in the GnomAD database, including 1,732 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 0.13 (1732 hom., cov: 32)
• Consequence: ARHGEF26 NM_015595.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.668
• Publications: 3 publications found

Genes affected

ARHGEF26 (HGNC:24490): (Rho guanine nucleotide exchange factor 26) This gene encodes a member of the Rho-guanine nucleotide exchange factor (Rho-GEF) family. These proteins regulate Rho GTPases by catalyzing the exchange of GDP for GTP. The encoded protein specifically activates RhoG and plays a role in the promotion of macropinocytosis. Underexpression of the encoded protein may be a predictive marker of chemoresistant disease. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2011]

LOC105374167 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF26	NM_015595.4	c.2301-3415G>A		intron_variant	Intron 12 of 14	ENST00000465093.6	NP_056410.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGEF26	ENST00000465093.6	c.2301-3415G>A		intron_variant	Intron 12 of 14	1	NM_015595.4	ENSP00000423418.1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20344 AN: 152050 Hom.: 1734 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.0583

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.0999

Gnomad OTH AF: 0.142

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

GnomAD4 genome AF: 0.134 AC: 20353 AN: 152166 Hom.: 1732 Cov.: 32 AF XY: 0.138 AC XY: 10238 AN XY: 74398

African (AFR) AF: 0.129 AC: 5368 AN: 41518

American (AMR) AF: 0.249 AC: 3807 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 582 AN: 3470

East Asian (EAS) AF: 0.384 AC: 1974 AN: 5136

South Asian (SAS) AF: 0.174 AC: 837 AN: 4816

European-Finnish (FIN) AF: 0.0583 AC: 619 AN: 10612

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.0999 AC: 6794 AN: 68006

Other (OTH) AF: 0.138 AC: 291 AN: 2104

Alfa AF: 0.119 Hom.: 2170

Bravo AF: 0.151

Asia WGS AF: 0.223 AC: 774 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.92
DANN	Benign	0.42
PhyloP100		-0.67
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: rs12491012; hg19: chr3-153967490;