11-120475651-G-A

Position:

• chr11-120475651-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015313.3(ARHGEF12):​c.3277+144G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 846,110 control chromosomes in the GnomAD database, including 14,076 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 (3118 hom., cov: 32)
  • Exomes 𝑓: 0.17 (10958 hom.)
• Consequence: ARHGEF12 NM_015313.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0100

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF12	NM_015313.3	c.3277+144G>A		intron_variant		ENST00000397843.7	NP_056128.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF12	ENST00000397843.7	c.3277+144G>A		intron_variant		1	NM_015313.3	ENSP00000380942	P4
ARHGEF12	ENST00000532993.5	c.2968+144G>A		intron_variant		1		ENSP00000432984
ARHGEF12	ENST00000356641.7	c.3220+144G>A		intron_variant		5		ENSP00000349056	A1
ARHGEF12	ENST00000529970.5	n.3411+144G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29826 AN: 151954 Hom.: 3113 Cov.: 32

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.0451

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.170

GnomAD4 exome AF: 0.172 AC: 119139 AN: 694038 Hom.: 10958 AF XY: 0.172 AC XY: 60515 AN XY: 351458

Gnomad4 AFR exome AF: 0.246

Gnomad4 AMR exome AF: 0.186

Gnomad4 ASJ exome AF: 0.175

Gnomad4 EAS exome AF: 0.224

Gnomad4 SAS exome AF: 0.212

Gnomad4 FIN exome AF: 0.226

Gnomad4 NFE exome AF: 0.159

Gnomad4 OTH exome AF: 0.175

GnomAD4 genome AF: 0.196 AC: 29855 AN: 152072 Hom.: 3118 Cov.: 32 AF XY: 0.200 AC XY: 14868 AN XY: 74340

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.235

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.237

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.167

Alfa AF: 0.167 Hom.: 4350

Bravo AF: 0.192

Asia WGS AF: 0.273 AC: 947 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.4
DANN	Benign	0.68

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: rs2276035; hg19: chr11-120346360;