rs11217878

chr11-120469674-G-Achr11-120469674-G-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF12	NM_015313.3	c.2955+286G>A		intron_variant		ENST00000397843.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF12	ENST00000397843.7	c.2955+286G>A		intron_variant		1	NM_015313.3	P4

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

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.235

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.166

Alfa AF: 0.175 Hom.: 1120

Bravo AF: 0.193

Asia WGS AF: 0.275 AC: 954 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	9.2
Dann	Benign	0.79

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: rs11217878; hg19: chr11-120340383;