Variant 14-21074594-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_018071.5(ARHGEF40):c.864G>A(p.Ala288=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 1,565,868 control chromosomes in the GnomAD database, including 37,745 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3452 hom., cov: 33)

Exomes 𝑓: 0.21 ( 34293 hom. )

Consequence

ARHGEF40
NM_018071.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.77

Variant links:

Genes affected

ARHGEF40 (HGNC:25516): (Rho guanine nucleotide exchange factor 40) This gene encodes a protein similar to guanosine nucleotide exchange factors for Rho GTPases. The encoded protein contains in its C-terminus a GEF domain involved in exchange activity and a pleckstrin homology domain. Alternatively spliced transcripts that encode different proteins have been described. [provided by RefSeq, Mar 2014]

ARHGEF40 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 14-21074594-G-A is Benign according to our data. Variant chr14-21074594-G-A is described in ClinVar as [Benign]. Clinvar id is 1298042.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.77 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF40	NM_018071.5 linkuse as main transcript	c.864G>A	p.Ala288=	synonymous_variant	3/24	ENST00000298694.9	NP_060541.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF40	ENST00000298694.9 linkuse as main transcript	c.864G>A	p.Ala288=	synonymous_variant	3/24	2	NM_018071.5	ENSP00000298694	P1	Q8TER5-1

Frequencies

GnomAD3 genomes

AF:

0.199

AC:

30326

AN:

152042

Hom.:

3447

Cov.:

show subpopulations

Gnomad AFR

AF:

0.147

Gnomad AMI

AF:

0.202

Gnomad AMR

AF:

0.139

Gnomad ASJ

AF:

0.178

Gnomad EAS

AF:

0.490

Gnomad SAS

AF:

0.250

Gnomad FIN

AF:

0.337

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.199

Gnomad OTH

AF:

0.184

GnomAD3 exomes

AF:

0.231

AC:

42127

AN:

182034

Hom.:

5725

AF XY:

0.234

AC XY:

23063

AN XY:

98482

show subpopulations

Gnomad AFR exome

AF:

0.152

Gnomad AMR exome

AF:

0.133

Gnomad ASJ exome

AF:

0.170

Gnomad EAS exome

AF:

0.506

Gnomad SAS exome

AF:

0.234

Gnomad FIN exome

AF:

0.328

Gnomad NFE exome

AF:

0.210

Gnomad OTH exome

AF:

0.221

GnomAD4 exome

AF:

0.212

AC:

299252

AN:

1413708

Hom.:

34293

Cov.:

AF XY:

0.213

AC XY:

148560

AN XY:

698886

show subpopulations

Gnomad4 AFR exome

AF:

0.149

Gnomad4 AMR exome

AF:

0.129

Gnomad4 ASJ exome

AF:

0.174

Gnomad4 EAS exome

AF:

0.512

Gnomad4 SAS exome

AF:

0.233

Gnomad4 FIN exome

AF:

0.319

Gnomad4 NFE exome

AF:

0.200

Gnomad4 OTH exome

AF:

0.212

GnomAD4 genome

AF:

0.200

AC:

30356

AN:

152160

Hom.:

3452

Cov.:

AF XY:

0.209

AC XY:

15574

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.148

Gnomad4 AMR

AF:

0.139

Gnomad4 ASJ

AF:

0.178

Gnomad4 EAS

AF:

0.490

Gnomad4 SAS

AF:

0.251

Gnomad4 FIN

AF:

0.337

Gnomad4 NFE

AF:

0.199

Gnomad4 OTH

AF:

0.184

Alfa

AF:

0.192

Hom.:

534

Bravo

AF:

0.182

Asia WGS

AF:

0.335

AC:

1166

AN:

3478

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	GeneDx	Oct 29, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.28

DANN

Benign

0.89

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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