Variant 7-144187123-G-C 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_001003702.3(ARHGEF35):c.1261C>G(p.Leu421Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 15 hom., cov: 20)

Exomes 𝑓: 0.0039 ( 212 hom. )

Failed GnomAD Quality Control

Consequence

ARHGEF35
NM_001003702.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.15

Variant links:

Genes affected

ARHGEF35 (HGNC:33846): (Rho guanine nucleotide exchange factor 35)

ARHGEF35 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=0.004467815).

BP6

Variant 7-144187123-G-C is Benign according to our data. Variant chr7-144187123-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2658123.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF35	NM_001003702.3 linkuse as main transcript	c.1261C>G	p.Leu421Val	missense_variant	2/2	ENST00000378115.3	NP_001003702.2	A5YM69
ARHGEF35	NM_001368318.1 linkuse as main transcript	c.1261C>G	p.Leu421Val	missense_variant	2/2		NP_001355247.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF35	ENST00000378115.3 linkuse as main transcript	c.1261C>G	p.Leu421Val	missense_variant	2/2	1	NM_001003702.3	ENSP00000367355.3		A5YM69
ARHGEF35	ENST00000688754.1 linkuse as main transcript	c.1261C>G	p.Leu421Val	missense_variant	2/2			ENSP00000510684.1		A5YM69

Frequencies

GnomAD3 genomes

AF:

0.00276

AC:

369

AN:

133936

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000950

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00155

Gnomad ASJ

AF:

0.00302

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000448

Gnomad FIN

AF:

0.00242

Gnomad MID

AF:

0.00671

Gnomad NFE

AF:

0.00446

Gnomad OTH

AF:

0.00609

GnomAD3 exomes

AF:

0.00344

AC:

719

AN:

208854

Hom.:

AF XY:

0.00353

AC XY:

401

AN XY:

113502

show subpopulations

Gnomad AFR exome

AF:

0.000597

Gnomad AMR exome

AF:

0.00235

Gnomad ASJ exome

AF:

0.00277

Gnomad EAS exome

AF:

0.000115

Gnomad SAS exome

AF:

0.00117

Gnomad FIN exome

AF:

0.00288

Gnomad NFE exome

AF:

0.00573

Gnomad OTH exome

AF:

0.00485

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00390

AC:

5435

AN:

1394438

Hom.:

212

Cov.:

AF XY:

0.00383

AC XY:

2656

AN XY:

694088

show subpopulations

Gnomad4 AFR exome

AF:

0.000901

Gnomad4 AMR exome

AF:

0.00237

Gnomad4 ASJ exome

AF:

0.00230

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.000879

Gnomad4 FIN exome

AF:

0.00338

Gnomad4 NFE exome

AF:

0.00447

Gnomad4 OTH exome

AF:

0.00396

GnomAD4 genome

AF:

0.00275

AC:

368

AN:

134050

Hom.:

Cov.:

AF XY:

0.00242

AC XY:

158

AN XY:

65182

show subpopulations

Gnomad4 AFR

AF:

0.000947

Gnomad4 AMR

AF:

0.00155

Gnomad4 ASJ

AF:

0.00302

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000448

Gnomad4 FIN

AF:

0.00242

Gnomad4 NFE

AF:

0.00444

Gnomad4 OTH

AF:

0.00601

Alfa

AF:

0.00177

Hom.:

ESP6500AA

AF:

0.000962

AC:

ESP6500EA

AF:

0.00410

AC:

ExAC

AF:

0.00418

AC:

488

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

ARHGEF35: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.0080

DANN

Benign

0.72

DEOGEN2

Benign

0.039

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0060

LIST_S2

Benign

0.39

MetaRNN

Benign

0.0045

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PROVEAN

Benign

-1.7

REVEL

Benign

0.064

Sift

Benign

0.11

Sift4G

Benign

0.72

Polyphen

0.0

Vest4

0.049

MVP

0.048

MPC

1.2

ClinPred

0.0045

GERP RS

-4.7

Varity_R

0.065

gMVP

0.013

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