11-120377784-A-G

Position:

• chr11-120377784-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ARHGEF12	NM_015313.3	c.33-28334A>G		intron_variant		ENST00000397843.7	NP_056128.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF12	ENST00000397843.7	c.33-28334A>G		intron_variant		1	NM_015313.3	ENSP00000380942.2
ARHGEF12	ENST00000356641.7	c.33-28334A>G		intron_variant		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

Gnomad4 AFR AF: 0.0239

Gnomad4 AMR AF: 0.0551

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.166

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.0778

Alfa AF: 0.102 Hom.: 114

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs58073046; hg19: chr11-120248493;