chr1-156984592-T-C

Position:

• chr1-156984592-T-C

Variant summary

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

The NM_198236.3(ARHGEF11):​c.125-155A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 151,998 control chromosomes in the GnomAD database, including 17,331 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 0.47 (17331 hom., cov: 31)
• Consequence: ARHGEF11 NM_198236.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.60

Genes affected

ARHGEF11 (HGNC:14580): (Rho guanine nucleotide exchange factor 11) Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli that work through G protein coupled receptors. The encoded protein may form a complex with G proteins and stimulate Rho-dependent signals. A similar protein in rat interacts with glutamate transporter EAAT4 and modulates its glutamate transport activity. Expression of the rat protein induces the reorganization of the actin cytoskeleton and its overexpression induces the formation of membrane ruffling and filopodia. Two alternative transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF11	NM_198236.3	c.125-155A>G		intron_variant		ENST00000368194.8	NP_937879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF11	ENST00000368194.8	c.125-155A>G		intron_variant		1	NM_198236.3	ENSP00000357177.3
ARHGEF11	ENST00000361409.2	c.125-155A>G		intron_variant		1		ENSP00000354644.2

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70775 AN: 151882 Hom.: 17287 Cov.: 31

Gnomad AFR AF: 0.560

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.802

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.457

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

GnomAD4 genome AF: 0.466 AC: 70873 AN: 151998 Hom.: 17331 Cov.: 31 AF XY: 0.471 AC XY: 34980 AN XY: 74284

Gnomad4 AFR AF: 0.561

Gnomad4 AMR AF: 0.497

Gnomad4 ASJ AF: 0.413

Gnomad4 EAS AF: 0.802

Gnomad4 SAS AF: 0.470

Gnomad4 FIN AF: 0.435

Gnomad4 NFE AF: 0.386

Gnomad4 OTH AF: 0.463

Alfa AF: 0.353 Hom.: 1716

Bravo AF: 0.477

Asia WGS AF: 0.648 AC: 2255 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.018
DANN	Benign	0.26

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: rs6427340; hg19: chr1-156954384;