Variant 7-66805218-A-G 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_014504.3(RABGEF1):c.899A>G(p.Asn300Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000471 in 1,614,160 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0022 ( 2 hom., cov: 31)

Exomes 𝑓: 0.00029 ( 3 hom. )

Consequence

RABGEF1
NM_014504.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.53

Variant links:

Genes affected

RABGEF1 (HGNC:17676): (RAB guanine nucleotide exchange factor 1) RABGEF1 forms a complex with rabaptin-5 (RABPT5; MIM 603616) that is required for endocytic membrane fusion, and it serves as a specific guanine nucleotide exchange factor (GEF) for RAB5 (RAB5A; MIM 179512) (Horiuchi et al., 1997 [PubMed 9323142]).[supplied by OMIM, Mar 2010]

RABGEF1 links:

ENSG00000284461 (HGNC:):

ENSG00000284461 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=0.007992923).

BP6

Variant 7-66805218-A-G is Benign according to our data. Variant chr7-66805218-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 732649.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RABGEF1	NM_014504.3 linkuse as main transcript	c.899A>G	p.Asn300Ser	missense_variant	8/9	ENST00000284957.9	NP_055319.1	Q9UJ41-2A0A024RDL6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RABGEF1	ENST00000284957.9 linkuse as main transcript	c.899A>G	p.Asn300Ser	missense_variant	8/9	1	NM_014504.3	ENSP00000284957.4	Q9UJ41-2
ENSG00000284461	ENST00000503687.2 linkuse as main transcript	n.*851A>G		non_coding_transcript_exon_variant	12/13	2		ENSP00000421074.1	E9PHB8
ENSG00000284461	ENST00000503687.2 linkuse as main transcript	n.*851A>G		3_prime_UTR_variant	12/13	2		ENSP00000421074.1	E9PHB8

Frequencies

GnomAD3 genomes

AF:

0.00219

AC:

334

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00765

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000656

AC:

165

AN:

251480

Hom.:

AF XY:

0.000493

AC XY:

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.00855

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000879

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000291

AC:

426

AN:

1461842

Hom.:

Cov.:

AF XY:

0.000276

AC XY:

201

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.00914

Gnomad4 AMR exome

AF:

0.000470

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000648

Gnomad4 OTH exome

AF:

0.000315

GnomAD4 genome

AF:

0.00220

AC:

335

AN:

152318

Hom.:

Cov.:

AF XY:

0.00200

AC XY:

149

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00765

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000597

Hom.:

Bravo

AF:

0.00260

ESP6500AA

AF:

0.00794

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000824

AC:

100

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

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

Labcorp Genetics (formerly Invitae), Labcorp

May 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.81

DEOGEN2

Benign

0.011

T;.;.;.;.;T

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.53

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.87

D;D;.;D;D;D

MetaRNN

Benign

0.0080

T;T;T;T;T;T

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.38

.;.;N;N;.;N

REVEL

Benign

0.083

Sift

Benign

0.47

.;.;T;T;.;T

Sift4G

Benign

0.68

T;T;T;T;T;T

Vest4

0.093

MVP

0.37

MPC

0.17

ClinPred

0.0028

GERP RS

0.086

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.27

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