Variant 4-154798037-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000281722.8(RBM46):c.378T>G(p.Ile126Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0197 in 1,613,818 control chromosomes in the GnomAD database, including 751 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.018 ( 76 hom., cov: 32)

Exomes 𝑓: 0.020 ( 675 hom. )

Consequence

RBM46
ENST00000281722.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.62

Variant links:

Genes affected

RBM46 (HGNC:28401): (RNA binding motif protein 46) Predicted to enable mRNA binding activity. Predicted to act upstream of or within mRNA stabilization and trophectodermal cell differentiation. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

RBM46 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00208053).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM46	NM_144979.5 linkuse as main transcript	c.378T>G	p.Ile126Met	missense_variant	3/5	ENST00000281722.8	NP_659416.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM46	ENST00000281722.8 linkuse as main transcript	c.378T>G	p.Ile126Met	missense_variant	3/5	1	NM_144979.5	ENSP00000281722	A1	Q8TBY0-1
RBM46	ENST00000514866.5 linkuse as main transcript	c.378T>G	p.Ile126Met	missense_variant	3/6	2		ENSP00000424500	P4	Q8TBY0-3
RBM46	ENST00000510397.5 linkuse as main transcript	c.378T>G	p.Ile126Met	missense_variant	3/5	2		ENSP00000422813		Q8TBY0-2
RBM46	ENST00000512640.1 linkuse as main transcript	c.378T>G	p.Ile126Met	missense_variant	3/3	4		ENSP00000426672

Frequencies

GnomAD3 genomes

AF:

0.0182

AC:

2769

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0147

Gnomad ASJ

AF:

0.0161

Gnomad EAS

AF:

0.130

Gnomad SAS

AF:

0.0207

Gnomad FIN

AF:

0.0387

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0163

Gnomad OTH

AF:

0.0177

GnomAD3 exomes

AF:

0.0268

AC:

6734

AN:

251004

Hom.:

212

AF XY:

0.0268

AC XY:

3632

AN XY:

135700

show subpopulations

Gnomad AFR exome

AF:

0.00377

Gnomad AMR exome

AF:

0.0198

Gnomad ASJ exome

AF:

0.0173

Gnomad EAS exome

AF:

0.137

Gnomad SAS exome

AF:

0.0190

Gnomad FIN exome

AF:

0.0348

Gnomad NFE exome

AF:

0.0160

Gnomad OTH exome

AF:

0.0251

GnomAD4 exome

AF:

0.0199

AC:

29040

AN:

1461528

Hom.:

675

Cov.:

AF XY:

0.0200

AC XY:

14519

AN XY:

727030

show subpopulations

Gnomad4 AFR exome

AF:

0.00350

Gnomad4 AMR exome

AF:

0.0197

Gnomad4 ASJ exome

AF:

0.0167

Gnomad4 EAS exome

AF:

0.147

Gnomad4 SAS exome

AF:

0.0196

Gnomad4 FIN exome

AF:

0.0340

Gnomad4 NFE exome

AF:

0.0151

Gnomad4 OTH exome

AF:

0.0216

GnomAD4 genome

AF:

0.0182

AC:

2771

AN:

152290

Hom.:

Cov.:

AF XY:

0.0197

AC XY:

1468

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00361

Gnomad4 AMR

AF:

0.0148

Gnomad4 ASJ

AF:

0.0161

Gnomad4 EAS

AF:

0.131

Gnomad4 SAS

AF:

0.0207

Gnomad4 FIN

AF:

0.0387

Gnomad4 NFE

AF:

0.0163

Gnomad4 OTH

AF:

0.0189

Alfa

AF:

0.0199

Hom.:

120

Bravo

AF:

0.0164

TwinsUK

AF:

0.0108

AC:

ALSPAC

AF:

0.0138

AC:

ESP6500AA

AF:

0.00409

AC:

ESP6500EA

AF:

0.0164

AC:

141

ExAC

AF:

0.0256

AC:

3107

Asia WGS

AF:

0.0620

AC:

216

AN:

3478

EpiCase

AF:

0.0163

EpiControl

AF:

0.0139

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.76

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

.;T;.;T

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.89

D;D;D;D

MetaRNN

Benign

0.0021

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

M;M;M;.

MutationTaster

Benign

0.000024

P;P;P

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-2.9

D;D;D;D

REVEL

Benign

0.27

Sift

Uncertain

0.013

D;D;D;D

Sift4G

Uncertain

0.018

D;D;D;T

Polyphen

0.99

.;D;.;.

Vest4

0.52

MPC

2.3

ClinPred

0.036

GERP RS

2.1

Varity_R

0.41

gMVP

0.81

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over