Variant chr13-111217879-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001354046.2(ARHGEF7):c.669C>T(p.Ser223=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,608,802 control chromosomes in the GnomAD database, including 145 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0083 ( 10 hom., cov: 33)

Exomes 𝑓: 0.011 ( 135 hom. )

Consequence

ARHGEF7
NM_001354046.2 splice_region, synonymous

Scores

Splicing: ADA: 0.0002760

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.654

Variant links:

Genes affected

ARHGEF7 (HGNC:15607): (Rho guanine nucleotide exchange factor 7) This gene encodes a protein that belongs to a family of cytoplasmic proteins that activate the Ras-like family of Rho proteins by exchanging bound GDP for GTP. It forms a complex with the small GTP binding protein Rac1 and recruits Rac1 to membrane ruffles and to focal adhesions. Multiple alternatively spliced transcript variants encoding different isoforms have been observed for this gene. [provided by RefSeq, Mar 2016]

ARHGEF7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 13-111217879-C-T is Benign according to our data. Variant chr13-111217879-C-T is described in ClinVar as [Benign]. Clinvar id is 769399.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.654 with no splicing effect.

BS2

High AC in GnomAd4 at 1258 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF7	NM_001354046.2 linkuse as main transcript	c.669C>T	p.Ser223=	splice_region_variant, synonymous_variant	5/22	ENST00000646102.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF7	ENST00000646102.2 linkuse as main transcript	c.669C>T	p.Ser223=	splice_region_variant, synonymous_variant	5/22		NM_001354046.2

Frequencies

GnomAD3 genomes

AF:

0.00827

AC:

1259

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00203

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0315

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0118

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00887

AC:

2194

AN:

247320

Hom.:

AF XY:

0.00867

AC XY:

1160

AN XY:

133838

show subpopulations

Gnomad AFR exome

AF:

0.00155

Gnomad AMR exome

AF:

0.00134

Gnomad ASJ exome

AF:

0.00121

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.000364

Gnomad FIN exome

AF:

0.0330

Gnomad NFE exome

AF:

0.0121

Gnomad OTH exome

AF:

0.00795

GnomAD4 exome

AF:

0.0110

AC:

15952

AN:

1456458

Hom.:

135

Cov.:

AF XY:

0.0107

AC XY:

7707

AN XY:

723526

show subpopulations

Gnomad4 AFR exome

AF:

0.00153

Gnomad4 AMR exome

AF:

0.00155

Gnomad4 ASJ exome

AF:

0.00135

Gnomad4 EAS exome

AF:

0.0000506

Gnomad4 SAS exome

AF:

0.000466

Gnomad4 FIN exome

AF:

0.0327

Gnomad4 NFE exome

AF:

0.0122

Gnomad4 OTH exome

AF:

0.00858

GnomAD4 genome

AF:

0.00826

AC:

1258

AN:

152344

Hom.:

Cov.:

AF XY:

0.00890

AC XY:

663

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00202

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.0315

Gnomad4 NFE

AF:

0.0118

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00995

Hom.:

Bravo

AF:

0.00582

Asia WGS

AF:

0.000866

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

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

1.3

DANN

Benign

0.90

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00028

dbscSNV1_RF

Benign

0.13

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