rs58073046

Variant names:

• chr11-120377784-A-G
• rs58073046
• NM_015313.3:c.33-28334A>G

Variant summary

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

The NM_015313.3(ARHGEF12):​c.33-28334A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0898 in 152,002 control chromosomes in the GnomAD database, including 859 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 0.090 (859 hom., cov: 32)
• Consequence: ARHGEF12 NM_015313.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740
• Publications: 19 publications found

Genes affected

ARHGEF12 (HGNC:14193): (Rho guanine nucleotide exchange factor 12) Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli working through G protein-coupled receptors. The encoded protein may form a complex with G proteins and stimulate Rho-dependent signals. This protein has been observed to form a myeloid/lymphoid fusion partner in acute myeloid leukemia. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF12	NM_015313.3	c.33-28334A>G		intron_variant	Intron 1 of 40	ENST00000397843.7	NP_056128.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGEF12	ENST00000397843.7	c.33-28334A>G		intron_variant	Intron 1 of 40	1	NM_015313.3	ENSP00000380942.2
ARHGEF12	ENST00000356641.7	c.33-28334A>G		intron_variant	Intron 1 of 39	5		ENSP00000349056.3

Frequencies

GnomAD3 genomes AF: 0.0898 AC: 13643 AN: 151884 Hom.: 855 Cov.: 32

Gnomad AFR AF: 0.0237

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0553

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.0796

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

GnomAD4 genome AF: 0.0898 AC: 13654 AN: 152002 Hom.: 859 Cov.: 32 AF XY: 0.0922 AC XY: 6852 AN XY: 74300

African (AFR) AF: 0.0239 AC: 992 AN: 41454

American (AMR) AF: 0.0551 AC: 842 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 513 AN: 3468

East Asian (EAS) AF: 0.166 AC: 859 AN: 5178

South Asian (SAS) AF: 0.207 AC: 998 AN: 4820

European-Finnish (FIN) AF: 0.122 AC: 1287 AN: 10510

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7926 AN: 67984

Other (OTH) AF: 0.0778 AC: 164 AN: 2108

Alfa AF: 0.0884 Hom.: 218

Bravo AF: 0.0779

Asia WGS AF: 0.191 AC: 664 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	13
DANN	Benign	0.97
PhyloP100		0.074
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: rs58073046; hg19: chr11-120248493;