Variant chr7-144187013-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The ENST00000378115.3(ARHGEF35):c.1371A>G(p.Arg457=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00388 in 143,130 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0039 ( 56 hom., cov: 21)

Exomes 𝑓: 0.0020 ( 519 hom. )

Failed GnomAD Quality Control

Consequence

ARHGEF35
ENST00000378115.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.266

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 7-144187013-T-C is Benign according to our data. Variant chr7-144187013-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2658122.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.266 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 56 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF35	NM_001003702.3 linkuse as main transcript	c.1371A>G	p.Arg457=	synonymous_variant	2/2	ENST00000378115.3	NP_001003702.2
ARHGEF35	NM_001368318.1 linkuse as main transcript	c.1371A>G	p.Arg457=	synonymous_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.1371A>G	p.Arg457=	synonymous_variant	2/2	1	NM_001003702.3	ENSP00000367355	P1
ARHGEF35	ENST00000688754.1 linkuse as main transcript	c.1371A>G	p.Arg457=	synonymous_variant	2/2			ENSP00000510684	P1

Frequencies

GnomAD3 genomes

AF:

0.00389

AC:

556

AN:

143016

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00596

Gnomad AMI

AF:

0.00899

Gnomad AMR

AF:

0.00287

Gnomad ASJ

AF:

0.00996

Gnomad EAS

AF:

0.00194

Gnomad SAS

AF:

0.00149

Gnomad FIN

AF:

0.00335

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00293

Gnomad OTH

AF:

0.00305

GnomAD3 exomes

AF:

0.00126

AC:

306

AN:

242026

Hom.:

AF XY:

0.00120

AC XY:

157

AN XY:

130990

show subpopulations

Gnomad AFR exome

AF:

0.00392

Gnomad AMR exome

AF:

0.00126

Gnomad ASJ exome

AF:

0.00377

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.000263

Gnomad FIN exome

AF:

0.00206

Gnomad NFE exome

AF:

0.000959

Gnomad OTH exome

AF:

0.00135

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00195

AC:

2724

AN:

1396548

Hom.:

519

Cov.:

AF XY:

0.00186

AC XY:

1294

AN XY:

695350

show subpopulations

Gnomad4 AFR exome

AF:

0.00526

Gnomad4 AMR exome

AF:

0.00204

Gnomad4 ASJ exome

AF:

0.00768

Gnomad4 EAS exome

AF:

0.00116

Gnomad4 SAS exome

AF:

0.000549

Gnomad4 FIN exome

AF:

0.00322

Gnomad4 NFE exome

AF:

0.00178

Gnomad4 OTH exome

AF:

0.00208

GnomAD4 genome

AF:

0.00388

AC:

555

AN:

143130

Hom.:

Cov.:

AF XY:

0.00398

AC XY:

278

AN XY:

69822

show subpopulations

Gnomad4 AFR

AF:

0.00591

Gnomad4 AMR

AF:

0.00287

Gnomad4 ASJ

AF:

0.00996

Gnomad4 EAS

AF:

0.00194

Gnomad4 SAS

AF:

0.00149

Gnomad4 FIN

AF:

0.00335

Gnomad4 NFE

AF:

0.00293

Gnomad4 OTH

AF:

0.00302

Alfa

AF:

0.00262

Hom.:

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

Sep 01, 2024

ARHGEF35: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

2.2

DANN

Benign

0.82

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