11-120403502-A-G

Variant names:

• chr11-120403502-A-G
• rs4938805
• NM_015313.3:c.33-2616A>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.33-2616A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 150,900 control chromosomes in the GnomAD database, including 17,131 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 0.46 (17131 hom., cov: 28)
• Consequence: ARHGEF12 NM_015313.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.10
• Publications: 5 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=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.626 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF12	NM_015313.3	MANE Select	c.33-2616A>G		intron	N/A	NP_056128.1
	ARHGEF12	NM_001198665.2		c.33-2616A>G		intron	N/A	NP_001185594.1
	ARHGEF12	NM_001301084.2		c.-277-2616A>G		intron	N/A	NP_001288013.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF12	ENST00000397843.7	TSL:1 MANE Select	c.33-2616A>G		intron	N/A	ENSP00000380942.2
	ARHGEF12	ENST00000532993.5	TSL:1	c.-277-2616A>G		intron	N/A	ENSP00000432984.1
	ARHGEF12	ENST00000356641.7	TSL:5	c.33-2616A>G		intron	N/A	ENSP00000349056.3

Frequencies

GnomAD3 genomes AF: 0.463 AC: 69774 AN: 150784 Hom.: 17088 Cov.: 28

Gnomad AFR AF: 0.632

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.453

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.438

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

GnomAD4 genome AF: 0.463 AC: 69865 AN: 150900 Hom.: 17131 Cov.: 28 AF XY: 0.463 AC XY: 34070 AN XY: 73628

African (AFR) AF: 0.633 AC: 25931 AN: 40972

American (AMR) AF: 0.385 AC: 5845 AN: 15184

Ashkenazi Jewish (ASJ) AF: 0.453 AC: 1571 AN: 3468

East Asian (EAS) AF: 0.304 AC: 1558 AN: 5126

South Asian (SAS) AF: 0.471 AC: 2246 AN: 4766

European-Finnish (FIN) AF: 0.444 AC: 4586 AN: 10330

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.395 AC: 26772 AN: 67758

Other (OTH) AF: 0.434 AC: 908 AN: 2094

Alfa AF: 0.260 Hom.: 647

Bravo AF: 0.462

Asia WGS AF: 0.449 AC: 1561 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.14
DANN	Benign	0.11
PhyloP100		-3.1
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: rs4938805; hg19: chr11-120274211;