Variant chr1-16204768-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_153213.5(ARHGEF19):c.1898G>A(p.Arg633Gln) variant causes a missense change. The variant allele was found at a frequency of 0.012 in 1,599,034 control chromosomes in the GnomAD database, including 155 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0092 ( 10 hom., cov: 33)

Exomes 𝑓: 0.012 ( 145 hom. )

Consequence

ARHGEF19
NM_153213.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.83

Variant links:

Genes affected

ARHGEF19 (HGNC:26604): (Rho guanine nucleotide exchange factor 19) Guanine nucleotide exchange factors (GEFs) such as ARHGEF19 accelerate the GTPase activity of Rho GTPases (see RHOA, MIM 165390).[supplied by OMIM, Dec 2008]

ARHGEF19 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006009549).

BP6

Variant 1-16204768-C-T is Benign according to our data. Variant chr1-16204768-C-T is described in ClinVar as [Benign]. Clinvar id is 786848.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF19	NM_153213.5 linkuse as main transcript	c.1898G>A	p.Arg633Gln	missense_variant	12/16	ENST00000270747.8
ARHGEF19	XM_011540706.4 linkuse as main transcript	c.1898G>A	p.Arg633Gln	missense_variant	13/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF19	ENST00000270747.8 linkuse as main transcript	c.1898G>A	p.Arg633Gln	missense_variant	12/16	1	NM_153213.5	P1	Q8IW93-1
ARHGEF19	ENST00000478117.5 linkuse as main transcript	n.825G>A		non_coding_transcript_exon_variant	7/11	1
ARHGEF19	ENST00000449495.1 linkuse as main transcript			downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00924

AC:

1406

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00258

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.00818

Gnomad ASJ

AF:

0.0300

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.0109

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0132

Gnomad OTH

AF:

0.00907

GnomAD3 exomes

AF:

0.00962

AC:

2354

AN:

244670

Hom.:

AF XY:

0.00972

AC XY:

1286

AN XY:

132242

show subpopulations

Gnomad AFR exome

AF:

0.00210

Gnomad AMR exome

AF:

0.00482

Gnomad ASJ exome

AF:

0.0325

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00331

Gnomad FIN exome

AF:

0.00903

Gnomad NFE exome

AF:

0.0134

Gnomad OTH exome

AF:

0.0137

GnomAD4 exome

AF:

0.0123

AC:

17788

AN:

1446752

Hom.:

145

Cov.:

AF XY:

0.0120

AC XY:

8585

AN XY:

717412

show subpopulations

Gnomad4 AFR exome

AF:

0.00260

Gnomad4 AMR exome

AF:

0.00495

Gnomad4 ASJ exome

AF:

0.0327

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00363

Gnomad4 FIN exome

AF:

0.00938

Gnomad4 NFE exome

AF:

0.0137

Gnomad4 OTH exome

AF:

0.0113

GnomAD4 genome

AF:

0.00923

AC:

1405

AN:

152282

Hom.:

Cov.:

AF XY:

0.00908

AC XY:

676

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00257

Gnomad4 AMR

AF:

0.00817

Gnomad4 ASJ

AF:

0.0300

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.0109

Gnomad4 NFE

AF:

0.0132

Gnomad4 OTH

AF:

0.00898

Alfa

AF:

0.0138

Hom.:

Bravo

AF:

0.00872

TwinsUK

AF:

0.0140

AC:

ALSPAC

AF:

0.0140

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.0134

AC:

115

ExAC

AF:

0.00937

AC:

1137

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.052

Eigen

Benign

-0.061

Eigen_PC

Benign

0.029

FATHMM_MKL

Uncertain

0.85

LIST_S2

Pathogenic

0.99

MetaRNN

Benign

0.0060

MetaSVM

Benign

-0.83

MutationAssessor

Benign

1.6

MutationTaster

Benign

0.99

D;D

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.11

Sift

Uncertain

0.024

Sift4G

Uncertain

0.038

Polyphen

0.16

Vest4

0.32

MVP

0.68

MPC

0.34

ClinPred

0.039

GERP RS

3.5

Varity_R

0.19

gMVP

0.56

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over