Variant chr19-40780072-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The ENST00000357052.8(RAB4B):c.70C>G(p.Leu24Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000268 in 1,611,448 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00028 ( 2 hom. )

Consequence

RAB4B
ENST00000357052.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.61

Variant links:

Genes affected

RAB4B (HGNC:9782): (RAB4B, member RAS oncogene family) Predicted to enable G protein activity and GTP binding activity. Involved in glucose import. Located in insulin-responsive compartment; perinuclear region of cytoplasm; and recycling endosome. [provided by Alliance of Genome Resources, Apr 2022]

RAB4B links:

MIA-RAB4B (HGNC:):

MIA-RAB4B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RAB4B	NM_016154.5 linkuse as main transcript	c.70C>G	p.Leu24Val	missense_variant	2/8	ENST00000357052.8	NP_057238.3
MIA-RAB4B	NR_037775.1 linkuse as main transcript	n.432C>G		non_coding_transcript_exon_variant	4/10
RAB4B-EGLN2	NR_037791.1 linkuse as main transcript	n.227C>G		non_coding_transcript_exon_variant	2/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB4B	ENST00000357052.8 linkuse as main transcript	c.70C>G	p.Leu24Val	missense_variant	2/8	1	NM_016154.5	ENSP00000349560	P1	P61018-1
	ENST00000595728.2 linkuse as main transcript	n.992-181G>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152042

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000412

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000163

AC:

AN:

251458

Hom.:

AF XY:

0.000199

AC XY:

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000343

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000275

AC:

402

AN:

1459406

Hom.:

Cov.:

AF XY:

0.000270

AC XY:

196

AN XY:

726226

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000351

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.000197

AC:

AN:

152042

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74270

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000412

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000229

Hom.:

Bravo

AF:

0.000147

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000132

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000356

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2023

The c.70C>G (p.L24V) alteration is located in exon 2 (coding exon 2) of the RAB4B gene. This alteration results from a C to G substitution at nucleotide position 70, causing the leucine (L) at amino acid position 24 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Pathogenic

0.29

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.51

D;D

Eigen

Benign

0.11

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.97

.;D

M_CAP

Uncertain

0.13

MetaRNN

Uncertain

0.63

D;D

MetaSVM

Uncertain

0.27

MutationAssessor

Uncertain

2.8

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-1.6

.;N

REVEL

Pathogenic

0.69

Sift

Benign

0.043

.;D

Sift4G

Benign

0.068

T;T

Polyphen

0.073

B;B

Vest4

0.78

MVP

0.98

MPC

0.35

ClinPred

0.099

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.51

gMVP

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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