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

Variant summary

Our verdict is Benign. The variant received -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. 16/21 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

Publications

52 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGEF11	ENST00000368194.8 link	c.4400A>G	p.His1467Arg	missense_variant	Exon 39 of 41	1	NM_198236.3	ENSP00000357177.3

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

GnomAD2 exomes

AF:

0.641

AC:

160920

AN:

251118

AF XY:

0.633

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 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

African (AFR)

AF:

0.850

AC:

28467

AN:

33480

American (AMR)

AF:

0.737

AC:

32948

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.631

AC:

16490

AN:

26124

East Asian (EAS)

AF:

0.866

AC:

34373

AN:

39700

South Asian (SAS)

AF:

0.697

AC:

60139

AN:

86244

European-Finnish (FIN)

AF:

0.560

AC:

29894

AN:

53398

Middle Eastern (MID)

AF:

0.555

AC:

3198

AN:

5762

European-Non Finnish (NFE)

AF:

0.537

AC:

596871

AN:

1111900

Other (OTH)

AF:

0.604

AC:

36450

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

20336

40672

61008

81344

101680

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17222

34444

51666

68888

86110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.656

AC:

99795

AN:

152038

Hom.:

34133

Cov.:

AF XY:

0.659

AC XY:

48973

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.838

AC:

34754

AN:

41468

American (AMR)

AF:

0.685

AC:

10481

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.638

AC:

2214

AN:

3472

East Asian (EAS)

AF:

0.862

AC:

4436

AN:

5146

South Asian (SAS)

AF:

0.711

AC:

3429

AN:

4822

European-Finnish (FIN)

AF:

0.556

AC:

5877

AN:

10578

Middle Eastern (MID)

AF:

0.527

AC:

155

AN:

294

European-Non Finnish (NFE)

AF:

0.539

AC:

36621

AN:

67950

Other (OTH)

AF:

0.656

AC:

1382

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1647

3295

4942

6590

8237

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

790

1580

2370

3160

3950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.590

Hom.:

92142

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

(source)

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

PhyloP100

-0.45

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

Mutation Taster

=91/9

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over