Variant 18-9517223-G-A 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_006788.4(RALBP1):c.623G>A(p.Arg208Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000588 in 1,612,810 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0031 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00033 ( 0 hom. )

Consequence

RALBP1
NM_006788.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.86

Variant links:

Genes affected

RALBP1 (HGNC:9841): (ralA binding protein 1) RALBP1 plays a role in receptor-mediated endocytosis and is a downstream effector of the small GTP-binding protein RAL (see RALA; MIM 179550). Small G proteins, such as RAL, have GDP-bound inactive and GTP-bound active forms, which shift from the inactive to the active state through the action of RALGDS (MIM 601619), which in turn is activated by RAS (see HRAS; MIM 190020) (summary by Feig, 2003 [PubMed 12888294]).[supplied by OMIM, Nov 2010]

RALBP1 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=0.005190909).

BP6

Variant 18-9517223-G-A is Benign according to our data. Variant chr18-9517223-G-A is described in ClinVar as [Benign]. Clinvar id is 784544.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RALBP1	NM_006788.4 linkuse as main transcript	c.623G>A	p.Arg208Gln	missense_variant	3/10	ENST00000383432.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
RALBP1	ENST00000383432.8 linkuse as main transcript	c.623G>A	p.Arg208Gln	missense_variant	3/10	1	NM_006788.4	P1
RALBP1	ENST00000019317.8 linkuse as main transcript	c.623G>A	p.Arg208Gln	missense_variant	3/10	1		P1
RALBP1	ENST00000609094.2 linkuse as main transcript	c.623G>A	p.Arg208Gln	missense_variant	3/3	2
RALBP1	ENST00000458039.3 linkuse as main transcript			downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00308

AC:

468

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0107

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000917

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000793

AC:

198

AN:

249540

Hom.:

AF XY:

0.000549

AC XY:

AN XY:

134898

show subpopulations

Gnomad AFR exome

AF:

0.0110

Gnomad AMR exome

AF:

0.000324

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000133

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.000492

GnomAD4 exome

AF:

0.000327

AC:

478

AN:

1460506

Hom.:

Cov.:

AF XY:

0.000279

AC XY:

203

AN XY:

726568

show subpopulations

Gnomad4 AFR exome

AF:

0.0122

Gnomad4 AMR exome

AF:

0.000316

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000582

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000900

Gnomad4 OTH exome

AF:

0.000696

GnomAD4 genome

AF:

0.00309

AC:

470

AN:

152304

Hom.:

Cov.:

AF XY:

0.00291

AC XY:

217

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0108

Gnomad4 AMR

AF:

0.000916

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000543

Hom.:

Bravo

AF:

0.00337

ESP6500AA

AF:

0.00931

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000980

AC:

119

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

Invitae

Jan 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.093

T;.;T

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.16

FATHMM_MKL

Uncertain

0.87

MetaRNN

Benign

0.0052

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.29

N;.;N

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.22

PROVEAN

Benign

0.81

N;.;N

REVEL

Benign

0.046

Sift

Benign

0.52

T;.;T

Sift4G

Benign

0.39

T;.;T

Polyphen

0.013

B;.;B

Vest4

0.15

MVP

0.29

MPC

0.57

ClinPred

0.018

GERP RS

4.2

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.1

Varity_R

0.17

gMVP

0.11

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