11-120403502-A-G

Position:

• chr11-120403502-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.33-2616A>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

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=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF12	NM_015313.3	c.33-2616A>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.33-2616A>G		intron_variant		1	NM_015313.3	ENSP00000380942	P4
ARHGEF12	ENST00000532993.5	c.-277-2616A>G		intron_variant		1		ENSP00000432984
ARHGEF12	ENST00000356641.7	c.33-2616A>G		intron_variant		5		ENSP00000349056	A1
ARHGEF12	ENST00000529970.5	n.167-2616A>G		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.633

Gnomad4 AMR AF: 0.385

Gnomad4 ASJ AF: 0.453

Gnomad4 EAS AF: 0.304

Gnomad4 SAS AF: 0.471

Gnomad4 FIN AF: 0.444

Gnomad4 NFE AF: 0.395

Gnomad4 OTH AF: 0.434

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.14
DANN	Benign	0.11

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: rs4938805; hg19: chr11-120274211;