chr1-156937379-T-G

Position:

chr1-156937379-T-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_198236.3(ARHGEF11):c.4310A>C(p.Gln1437Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000195 in 1,608,482 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 1 hom. )

Consequence

ARHGEF11
NM_198236.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -6.09

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013549507).

BS2

High AC in GnomAd4 at 28 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF11	NM_198236.3 linkuse as main transcript	c.4310A>C	p.Gln1437Pro	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.4310A>C	p.Gln1437Pro	missense_variant	39/41	1	NM_198236.3	ENSP00000357177.3	O15085-2
ARHGEF11	ENST00000361409.2 linkuse as main transcript	c.4190A>C	p.Gln1397Pro	missense_variant	38/40	1		ENSP00000354644.2	O15085-1
ARHGEF11	ENST00000487682.5 linkuse as main transcript	n.3262A>C		non_coding_transcript_exon_variant	8/10	2
ARHGEF11	ENST00000492592.1 linkuse as main transcript	n.544A>C		non_coding_transcript_exon_variant	4/5	3

Frequencies

GnomAD3 genomes

AF:

0.000184

AC:

AN:

152054

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000192

AC:

AN:

244206

Hom.:

AF XY:

0.000190

AC XY:

AN XY:

131670

show subpopulations

Gnomad AFR exome

AF:

0.000617

Gnomad AMR exome

AF:

0.000267

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000472

Gnomad NFE exome

AF:

0.000199

Gnomad OTH exome

AF:

0.000840

GnomAD4 exome

AF:

0.000196

AC:

285

AN:

1456310

Hom.:

Cov.:

AF XY:

0.000191

AC XY:

138

AN XY:

724016

show subpopulations

Gnomad4 AFR exome

AF:

0.000629

Gnomad4 AMR exome

AF:

0.000363

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000376

Gnomad4 NFE exome

AF:

0.000198

Gnomad4 OTH exome

AF:

0.000283

GnomAD4 genome

AF:

0.000184

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.0000979

Hom.:

Bravo

AF:

0.000246

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000181

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

Nov 27, 2024

The c.4190A>C (p.Q1397P) alteration is located in exon 38 (coding exon 38) of the ARHGEF11 gene. This alteration results from a A to C substitution at nucleotide position 4190, causing the glutamine (Q) at amino acid position 1397 to be replaced by a proline (P). 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

0.060

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.57

CADD

Benign

0.0060

DANN

Benign

0.67

DEOGEN2

Benign

0.030

.;T

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.0057

LIST_S2

Benign

0.48

T;T

M_CAP

Benign

0.0071

MetaRNN

Benign

0.014

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.0

.;L

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.84

N;N

REVEL

Benign

0.094

Sift

Uncertain

0.020

D;D

Sift4G

Benign

0.31

T;T

Polyphen

0.0

B;B

Vest4

0.20

MVP

0.37

MPC

0.038

ClinPred

0.030

GERP RS

-10

Varity_R

0.11

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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