11-120469674-G-A

Variant names:

• chr11-120469674-G-A
• rs11217878
• NM_015313.3:c.2955+286G>A

Variant summary

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

The NM_015313.3(ARHGEF12):​c.2955+286G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,072 control chromosomes in the GnomAD database, including 3,121 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 0.20 (3121 hom., cov: 33)
• Consequence: ARHGEF12 NM_015313.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.905
• Publications: 9 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015313.3. 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
	ARHGEF12	NM_015313.3	MANE Select	c.2955+286G>A		intron	N/A	NP_056128.1
	ARHGEF12	NM_001198665.2		c.2898+286G>A		intron	N/A	NP_001185594.1
	ARHGEF12	NM_001301084.2		c.2646+286G>A		intron	N/A	NP_001288013.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF12	ENST00000397843.7	TSL:1 MANE Select	c.2955+286G>A		intron	N/A	ENSP00000380942.2
	ARHGEF12	ENST00000532993.5	TSL:1	c.2646+286G>A		intron	N/A	ENSP00000432984.1
	ARHGEF12	ENST00000356641.7	TSL:5	c.2898+286G>A		intron	N/A	ENSP00000349056.3

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29847 AN: 151954 Hom.: 3115 Cov.: 33

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.169

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

GnomAD4 genome AF: 0.196 AC: 29881 AN: 152072 Hom.: 3121 Cov.: 33 AF XY: 0.200 AC XY: 14864 AN XY: 74310

African (AFR) AF: 0.248 AC: 10305 AN: 41474

American (AMR) AF: 0.177 AC: 2703 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 597 AN: 3470

East Asian (EAS) AF: 0.235 AC: 1211 AN: 5162

South Asian (SAS) AF: 0.232 AC: 1118 AN: 4820

European-Finnish (FIN) AF: 0.235 AC: 2480 AN: 10540

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 11026 AN: 67990

Other (OTH) AF: 0.166 AC: 351 AN: 2114

Alfa AF: 0.175 Hom.: 1235

Bravo AF: 0.193

Asia WGS AF: 0.275 AC: 954 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.2
DANN	Benign	0.79
PhyloP100		0.91
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: rs11217878; hg19: chr11-120340383;