dbSNP rs79167802: RBM46:p.Ile126Met (chr4-154798037-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_144979.5(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
NM_144979.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.62

Publications

11 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RBM46	NM_144979.5 link	c.378T>G	p.Ile126Met	missense_variant	Exon 3 of 5	ENST00000281722.8	NP_659416.1	Q8TBY0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RBM46	ENST00000281722.8 link	c.378T>G	p.Ile126Met	missense_variant	Exon 3 of 5	1	NM_144979.5	ENSP00000281722.3	Q8TBY0-1
RBM46	ENST00000514866.5 link	c.378T>G	p.Ile126Met	missense_variant	Exon 3 of 6	2		ENSP00000424500.1	Q8TBY0-3
RBM46	ENST00000510397.5 link	c.378T>G	p.Ile126Met	missense_variant	Exon 3 of 5	2		ENSP00000422813.1	Q8TBY0-2
RBM46	ENST00000512640.1 link	c.378T>G	p.Ile126Met	missense_variant	Exon 3 of 3	4		ENSP00000426672.1	D6RF41

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

GnomAD2 exomes

AF:

0.0268

AC:

6734

AN:

251004

AF XY:

0.0268

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 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

African (AFR)

AF:

0.00350

AC:

117

AN:

33470

American (AMR)

AF:

0.0197

AC:

883

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.0167

AC:

436

AN:

26128

East Asian (EAS)

AF:

0.147

AC:

5847

AN:

39678

South Asian (SAS)

AF:

0.0196

AC:

1686

AN:

86120

European-Finnish (FIN)

AF:

0.0340

AC:

1818

AN:

53398

Middle Eastern (MID)

AF:

0.0199

AC:

115

AN:

5768

European-Non Finnish (NFE)

AF:

0.0151

AC:

16834

AN:

1111872

Other (OTH)

AF:

0.0216

AC:

1304

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

1557

3113

4670

6226

7783

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

722

1444

2166

2888

3610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0182

AC:

2771

AN:

152290

Hom.:

Cov.:

AF XY:

0.0197

AC XY:

1468

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.00361

AC:

150

AN:

41586

American (AMR)

AF:

0.0148

AC:

226

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0161

AC:

AN:

3472

East Asian (EAS)

AF:

0.131

AC:

677

AN:

5180

South Asian (SAS)

AF:

0.0207

AC:

100

AN:

4824

European-Finnish (FIN)

AF:

0.0387

AC:

410

AN:

10598

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0163

AC:

1108

AN:

68004

Other (OTH)

AF:

0.0189

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

139

279

418

558

697

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0191

Hom.:

223

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

(source)

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;.

PhyloP100

1.6

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

Mutation Taster

=86/14

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over