Variant 1-156937323-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_198236.3(ARHGEF11):c.4366A>G(p.Ser1456Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 1,613,488 control chromosomes in the GnomAD database, including 111,136 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 0.34 ( 9079 hom., cov: 31)

Exomes 𝑓: 0.37 ( 102057 hom. )

Consequence

ARHGEF11
NM_198236.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.10

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:

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=3.9103627E-4).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF11	NM_198236.3 linkuse as main transcript	c.4366A>G	p.Ser1456Gly	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.4366A>G	p.Ser1456Gly	missense_variant	39/41	1	NM_198236.3	ENSP00000357177.3	O15085-2
ARHGEF11	ENST00000361409.2 linkuse as main transcript	c.4246A>G	p.Ser1416Gly	missense_variant	38/40	1		ENSP00000354644.2	O15085-1
ARHGEF11	ENST00000487682.5 linkuse as main transcript	n.3318A>G		non_coding_transcript_exon_variant	8/10	2
ARHGEF11	ENST00000492592.1 linkuse as main transcript	n.600A>G		non_coding_transcript_exon_variant	4/5	3

Frequencies

GnomAD3 genomes

AF:

0.336

AC:

50969

AN:

151850

Hom.:

9074

Cov.:

show subpopulations

Gnomad AFR

AF:

0.224

Gnomad AMI

AF:

0.331

Gnomad AMR

AF:

0.443

Gnomad ASJ

AF:

0.399

Gnomad EAS

AF:

0.495

Gnomad SAS

AF:

0.485

Gnomad FIN

AF:

0.359

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.349

Gnomad OTH

AF:

0.361

GnomAD3 exomes

AF:

0.402

AC:

100829

AN:

250858

Hom.:

21501

AF XY:

0.401

AC XY:

54351

AN XY:

135604

show subpopulations

Gnomad AFR exome

AF:

0.227

Gnomad AMR exome

AF:

0.558

Gnomad ASJ exome

AF:

0.391

Gnomad EAS exome

AF:

0.496

Gnomad SAS exome

AF:

0.477

Gnomad FIN exome

AF:

0.367

Gnomad NFE exome

AF:

0.352

Gnomad OTH exome

AF:

0.387

GnomAD4 exome

AF:

0.369

AC:

539469

AN:

1461518

Hom.:

102057

Cov.:

AF XY:

0.372

AC XY:

270569

AN XY:

727062

show subpopulations

Gnomad4 AFR exome

AF:

0.219

Gnomad4 AMR exome

AF:

0.545

Gnomad4 ASJ exome

AF:

0.392

Gnomad4 EAS exome

AF:

0.469

Gnomad4 SAS exome

AF:

0.477

Gnomad4 FIN exome

AF:

0.365

Gnomad4 NFE exome

AF:

0.354

Gnomad4 OTH exome

AF:

0.371

GnomAD4 genome

AF:

0.335

AC:

50979

AN:

151970

Hom.:

9079

Cov.:

AF XY:

0.339

AC XY:

25198

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.224

Gnomad4 AMR

AF:

0.443

Gnomad4 ASJ

AF:

0.399

Gnomad4 EAS

AF:

0.495

Gnomad4 SAS

AF:

0.484

Gnomad4 FIN

AF:

0.359

Gnomad4 NFE

AF:

0.349

Gnomad4 OTH

AF:

0.357

Alfa

AF:

0.356

Hom.:

15195

Bravo

AF:

0.338

TwinsUK

AF:

0.352

AC:

1306

ALSPAC

AF:

0.361

AC:

1391

ESP6500AA

AF:

0.224

AC:

987

ESP6500EA

AF:

0.357

AC:

3067

ExAC

AF:

0.394

AC:

47792

Asia WGS

AF:

0.456

AC:

1587

AN:

3476

EpiCase

AF:

0.349

EpiControl

AF:

0.357

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.056

.;T

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.74

T;T

MetaRNN

Benign

0.00039

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

.;L

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.13

Sift

Benign

0.11

T;T

Sift4G

Uncertain

0.053

T;T

Polyphen

0.0030

B;B

Vest4

0.038

MPC

0.032

ClinPred

0.0037

GERP RS

0.50

Varity_R

0.10

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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