Variant 1-156937299-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_198236.3(ARHGEF11):c.4390A>G(p.Met1464Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ARHGEF11
NM_198236.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0700

Variant links:

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]

ARHGEF11 links:

LRRC71 (HGNC:26556): (leucine rich repeat containing 71)

LRRC71 links:

ARHGEF11 (HGNC:):

ARHGEF11 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.022279412).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF11	NM_198236.3 linkuse as main transcript	c.4390A>G	p.Met1464Val	missense_variant	39/41	ENST00000368194.8	NP_937879.1	O15085-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ARHGEF11	ENST00000368194.8 linkuse as main transcript	c.4390A>G	p.Met1464Val	missense_variant	39/41	1	NM_198236.3	ENSP00000357177.3	O15085-2
ARHGEF11	ENST00000361409.2 linkuse as main transcript	c.4270A>G	p.Met1424Val	missense_variant	38/40	1		ENSP00000354644.2	O15085-1
ARHGEF11	ENST00000487682.5 linkuse as main transcript	n.3342A>G		non_coding_transcript_exon_variant	8/10	2
ARHGEF11	ENST00000492592.1 linkuse as main transcript	n.624A>G		non_coding_transcript_exon_variant	4/5	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251286

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135826

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461738

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727174

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 29, 2022

The c.4270A>G (p.M1424V) alteration is located in exon 38 (coding exon 38) of the ARHGEF11 gene. This alteration results from a A to G substitution at nucleotide position 4270, causing the methionine (M) at amino acid position 1424 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.58

CADD

Benign

4.1

DANN

Benign

0.75

DEOGEN2

Benign

0.027

.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.63

T;T

M_CAP

Benign

0.0055

MetaRNN

Benign

0.022

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

.;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.34

N;N

REVEL

Benign

0.046

Sift

Benign

0.37

T;T

Sift4G

Benign

0.41

T;T

Polyphen

0.0

B;B

Vest4

0.19

MutPred

0.32

.;Gain of sheet (P = 0.0149);

MVP

0.34

MPC

0.034

ClinPred

0.012

GERP RS

-1.9

Varity_R

0.036

gMVP

0.21

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over