chr11-66669012-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000310046.9(RBM4B):​c.692C>T​(p.Ala231Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000452 in 1,614,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

RBM4B
ENST00000310046.9 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.32
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.15322894).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RBM4BNM_031492.4 linkuse as main transcriptc.692C>T p.Ala231Val missense_variant 3/4 ENST00000310046.9 NP_113680.1 Q9BQ04

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RBM4BENST00000310046.9 linkuse as main transcriptc.692C>T p.Ala231Val missense_variant 3/41 NM_031492.4 ENSP00000310471.4 Q9BQ04
RBM4BENST00000525754.5 linkuse as main transcriptc.692C>T p.Ala231Val missense_variant 2/32 ENSP00000433071.1 Q9BQ04
RBM4BENST00000524637 linkuse as main transcriptc.*296C>T 3_prime_UTR_variant 4/45 ENSP00000433113.1 E9PM61
RBM4BENST00000531969.5 linkuse as main transcriptc.413-3434C>T intron_variant 3 ENSP00000435239.1 E9PLB0

Frequencies

GnomAD3 genomes
AF:
0.000177
AC:
27
AN:
152214
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000555
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000875
AC:
22
AN:
251426
Hom.:
0
AF XY:
0.0000809
AC XY:
11
AN XY:
135888
show subpopulations
Gnomad AFR exome
AF:
0.000738
Gnomad AMR exome
AF:
0.000289
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000315
AC:
46
AN:
1461888
Hom.:
0
Cov.:
32
AF XY:
0.0000248
AC XY:
18
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.000806
Gnomad4 AMR exome
AF:
0.000201
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.000177
AC:
27
AN:
152214
Hom.:
0
Cov.:
32
AF XY:
0.000108
AC XY:
8
AN XY:
74356
show subpopulations
Gnomad4 AFR
AF:
0.000555
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000132
Hom.:
0
Bravo
AF:
0.000276
ESP6500AA
AF:
0.000455
AC:
2
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000494
AC:
6

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 submitterclinical testingAmbry GeneticsJan 03, 2024The c.692C>T (p.A231V) alteration is located in exon 3 (coding exon 2) of the RBM4B gene. This alteration results from a C to T substitution at nucleotide position 692, causing the alanine (A) at amino acid position 231 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
0.20
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.25
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.034
T;T
Eigen
Benign
-0.0082
Eigen_PC
Benign
0.18
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.84
.;T
M_CAP
Benign
0.0074
T
MetaRNN
Benign
0.15
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.2
L;L
MutationTaster
Benign
0.98
D;D;D;D
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
-0.63
N;N
REVEL
Benign
0.14
Sift
Benign
0.45
T;T
Sift4G
Benign
0.20
T;T
Polyphen
0.0010
B;B
Vest4
0.63
MVP
0.33
MPC
0.30
ClinPred
0.029
T
GERP RS
5.4
Varity_R
0.12
gMVP
0.36

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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.

Other links and lift over

dbSNP: rs371878027; hg19: chr11-66436483; API