Genetic Variant NM_198236.3:c.4400A>G (chr1-156937289-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_198236.3(ARHGEF11):c.4400A>G(p.His1467Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 1,613,742 control chromosomes in the GnomAD database, including 280,324 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.66 ( 34133 hom., cov: 31)

Exomes 𝑓: 0.57 ( 246191 hom. )

Consequence

ARHGEF11
NM_198236.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.452

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.671436E-7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF11	NM_198236.3 link	c.4400A>G	p.His1467Arg	missense_variant	Exon 39 of 41	ENST00000368194.8	NP_937879.1	O15085-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ARHGEF11	ENST00000368194.8 link	c.4400A>G	p.His1467Arg	missense_variant	Exon 39 of 41	1	NM_198236.3	ENSP00000357177.3	O15085-2
ARHGEF11	ENST00000361409.2 link	c.4280A>G	p.His1427Arg	missense_variant	Exon 38 of 40	1		ENSP00000354644.2	O15085-1
ARHGEF11	ENST00000487682.5 link	n.3352A>G		non_coding_transcript_exon_variant	Exon 8 of 10	2
ARHGEF11	ENST00000492592.1 link	n.634A>G		non_coding_transcript_exon_variant	Exon 4 of 5	3

Frequencies

GnomAD3 genomes

AF:

0.656

AC:

99668

AN:

151920

Hom.:

34062

Cov.:

show subpopulations

Gnomad AFR

AF:

0.838

Gnomad AMI

AF:

0.489

Gnomad AMR

AF:

0.685

Gnomad ASJ

AF:

0.638

Gnomad EAS

AF:

0.861

Gnomad SAS

AF:

0.712

Gnomad FIN

AF:

0.556

Gnomad MID

AF:

0.532

Gnomad NFE

AF:

0.539

Gnomad OTH

AF:

0.653

GnomAD3 exomes

AF:

0.641

AC:

160920

AN:

251118

Hom.:

53320

AF XY:

0.633

AC XY:

85932

AN XY:

135742

show subpopulations

Gnomad AFR exome

AF:

0.850

Gnomad AMR exome

AF:

0.740

Gnomad ASJ exome

AF:

0.633

Gnomad EAS exome

AF:

0.869

Gnomad SAS exome

AF:

0.703

Gnomad FIN exome

AF:

0.567

Gnomad NFE exome

AF:

0.543

Gnomad OTH exome

AF:

0.608

GnomAD4 exome

AF:

0.574

AC:

838830

AN:

1461704

Hom.:

246191

Cov.:

AF XY:

0.577

AC XY:

419700

AN XY:

727160

show subpopulations

Gnomad4 AFR exome

AF:

0.850

Gnomad4 AMR exome

AF:

0.737

Gnomad4 ASJ exome

AF:

0.631

Gnomad4 EAS exome

AF:

0.866

Gnomad4 SAS exome

AF:

0.697

Gnomad4 FIN exome

AF:

0.560

Gnomad4 NFE exome

AF:

0.537

Gnomad4 OTH exome

AF:

0.604

GnomAD4 genome

AF:

0.656

AC:

99795

AN:

152038

Hom.:

34133

Cov.:

AF XY:

0.659

AC XY:

48973

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.838

Gnomad4 AMR

AF:

0.685

Gnomad4 ASJ

AF:

0.638

Gnomad4 EAS

AF:

0.862

Gnomad4 SAS

AF:

0.711

Gnomad4 FIN

AF:

0.556

Gnomad4 NFE

AF:

0.539

Gnomad4 OTH

AF:

0.656

Alfa

AF:

0.575

Hom.:

63540

Bravo

AF:

0.674

TwinsUK

AF:

0.529

AC:

1963

ALSPAC

AF:

0.541

AC:

2086

ESP6500AA

AF:

0.840

AC:

3701

ESP6500EA

AF:

0.553

AC:

4757

ExAC

AF:

0.639

AC:

77584

Asia WGS

AF:

0.803

AC:

2792

AN:

3478

EpiCase

AF:

0.549

EpiControl

AF:

0.555

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.68

CADD

Benign

1.2

DANN

Benign

0.74

DEOGEN2

Benign

0.034

.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0039

LIST_S2

Benign

0.036

T;T

MetaRNN

Benign

5.7e-7

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.55

.;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.13

N;N

REVEL

Benign

0.048

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.023

MPC

0.038

ClinPred

0.0092

GERP RS

-1.6

Varity_R

0.022

gMVP

0.16

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over