Variant 11-66668980-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000310046.9(RBM4B):c.724A>G(p.Asn242Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000997 in 1,614,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

RBM4B
ENST00000310046.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.66

Variant links:

Genes affected

RBM4B (HGNC:28842): (RNA binding motif protein 4B) Enables RNA binding activity. Predicted to be involved in entrainment of circadian clock by photoperiod; mRNA splicing, via spliceosome; and regulation of gene expression. Predicted to act upstream of or within positive regulation of gene expression. Located in cytosol and nucleoplasm. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

RBM4B links:

RBM4B (HGNC:):

RBM4B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.057932615).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM4B	NM_031492.4 linkuse as main transcript	c.724A>G	p.Asn242Asp	missense_variant	3/4	ENST00000310046.9	NP_113680.1	Q9BQ04

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RBM4B	ENST00000310046.9 linkuse as main transcript	c.724A>G	p.Asn242Asp	missense_variant	3/4	1	NM_031492.4	ENSP00000310471.4	Q9BQ04
RBM4B	ENST00000525754.5 linkuse as main transcript	c.724A>G	p.Asn242Asp	missense_variant	2/3	2		ENSP00000433071.1	Q9BQ04
RBM4B	ENST00000524637 linkuse as main transcript	c.*328A>G		3_prime_UTR_variant	4/4	5		ENSP00000433113.1	E9PM61
RBM4B	ENST00000531969.5 linkuse as main transcript	c.413-3402A>G		intron_variant		3		ENSP00000435239.1	E9PLB0

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000557

AC:

AN:

251392

Hom.:

AF XY:

0.0000589

AC XY:

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.000114

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000105

AC:

154

AN:

1461864

Hom.:

Cov.:

AF XY:

0.000102

AC XY:

AN XY:

727234

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:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000135

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000889

Hom.:

Bravo

AF:

0.0000567

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000237

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

Feb 26, 2024

The c.724A>G (p.N242D) alteration is located in exon 3 (coding exon 2) of the RBM4B gene. This alteration results from a A to G substitution at nucleotide position 724, causing the asparagine (N) at amino acid position 242 to be replaced by an aspartic acid (D). 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

0.10

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.021

T;T

Eigen

Benign

-0.17

Eigen_PC

Benign

0.041

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.67

.;T

M_CAP

Benign

0.0024

MetaRNN

Benign

0.058

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

N;N

MutationTaster

Benign

1.0

D;D;N;N

PrimateAI

Uncertain

0.57

PROVEAN

Benign

0.68

N;N

REVEL

Benign

0.058

Sift

Benign

0.46

T;T

Sift4G

Benign

0.68

T;T

Polyphen

0.0

B;B

Vest4

0.12

MVP

0.26

MPC

0.34

ClinPred

0.072

GERP RS

5.9

Varity_R

0.094

gMVP

0.45

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