Variant chr11-120429739-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_015313.3(ARHGEF12):c.691C>T(p.Pro231Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000721 in 1,613,640 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0041 ( 7 hom., cov: 32)

Exomes 𝑓: 0.00037 ( 4 hom. )

Consequence

ARHGEF12
NM_015313.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.78

Variant links:

Genes affected

ARHGEF12 (HGNC:14193): (Rho guanine nucleotide exchange factor 12) Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli working through G protein-coupled receptors. The encoded protein may form a complex with G proteins and stimulate Rho-dependent signals. This protein has been observed to form a myeloid/lymphoid fusion partner in acute myeloid leukemia. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

ARHGEF12 links:

ARHGEF12 (HGNC:):

ARHGEF12 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004073918).

BP6

Variant 11-120429739-C-T is Benign according to our data. Variant chr11-120429739-C-T is described in ClinVar as [Benign]. Clinvar id is 787914.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 618 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF12	NM_015313.3 linkuse as main transcript	c.691C>T	p.Pro231Ser	missense_variant	10/41	ENST00000397843.7	NP_056128.1	Q9NZN5-1B4E2K6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ARHGEF12	ENST00000397843.7 linkuse as main transcript	c.691C>T	p.Pro231Ser	missense_variant	10/41	1	NM_015313.3	ENSP00000380942.2	Q9NZN5-1
ARHGEF12	ENST00000532993.5 linkuse as main transcript	c.382C>T	p.Pro128Ser	missense_variant	10/41	1		ENSP00000432984.1	E9PMR6
ARHGEF12	ENST00000356641.7 linkuse as main transcript	c.634C>T	p.Pro212Ser	missense_variant	9/40	5		ENSP00000349056.3	Q9NZN5-2
ARHGEF12	ENST00000529970.5 linkuse as main transcript	n.825C>T		non_coding_transcript_exon_variant	10/36	2

Frequencies

GnomAD3 genomes

AF:

0.00406

AC:

617

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0134

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00308

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00100

AC:

250

AN:

248778

Hom.:

AF XY:

0.000808

AC XY:

109

AN XY:

134932

show subpopulations

Gnomad AFR exome

AF:

0.0146

Gnomad AMR exome

AF:

0.000610

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000887

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.000374

AC:

546

AN:

1461390

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

205

AN XY:

726944

show subpopulations

Gnomad4 AFR exome

AF:

0.0136

Gnomad4 AMR exome

AF:

0.000783

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.000812

GnomAD4 genome

AF:

0.00406

AC:

618

AN:

152250

Hom.:

Cov.:

AF XY:

0.00419

AC XY:

312

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0134

Gnomad4 AMR

AF:

0.00307

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.000754

Hom.:

Bravo

AF:

0.00494

ESP6500AA

AF:

0.0103

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00133

AC:

160

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

.;T;T

Eigen

Benign

-0.031

Eigen_PC

Benign

0.12

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.79

T;T;T

MetaRNN

Benign

0.0041

T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.2

.;M;.

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-4.0

D;D;D

REVEL

Benign

0.054

Sift

Benign

0.093

T;T;T

Sift4G

Benign

0.073

T;T;T

Polyphen

0.10

B;B;.

Vest4

0.21

MVP

0.45

MPC

0.56

ClinPred

0.075

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.9

Varity_R

0.18

gMVP

0.43

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over