chr3-25174417-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001290216.3(RARB):​c.20C>T​(p.Ala7Val) variant causes a missense change. The variant allele was found at a frequency of 0.000377 in 1,352,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 8/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.00044 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00037 ( 0 hom. )

Consequence

RARB
NM_001290216.3 missense

Scores

5
11

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 5.75
Variant links:
Genes affected
RARB (HGNC:9865): (retinoic acid receptor beta) This gene encodes retinoic acid receptor beta, a member of the thyroid-steroid hormone receptor superfamily of nuclear transcriptional regulators. This receptor localizes to the cytoplasm and to subnuclear compartments. It binds retinoic acid, the biologically active form of vitamin A which mediates cellular signalling in embryonic morphogenesis, cell growth and differentiation. It is thought that this protein limits growth of many cell types by regulating gene expression. The gene was first identified in a hepatocellular carcinoma where it flanks a hepatitis B virus integration site. Alternate promoter usage and differential splicing result in multiple transcript variants. [provided by RefSeq, Mar 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.1353746).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RARBNM_001290216.3 linkuse as main transcriptc.20C>T p.Ala7Val missense_variant 4/11 NP_001277145.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RARBENST00000383772.9 linkuse as main transcriptc.20C>T p.Ala7Val missense_variant 5/125 ENSP00000373282 P10826-1
RARBENST00000686715.1 linkuse as main transcriptc.20C>T p.Ala7Val missense_variant 5/12 ENSP00000510539 P10826-1
RARBENST00000687353.1 linkuse as main transcriptc.20C>T p.Ala7Val missense_variant 6/13 ENSP00000508588 P10826-1

Frequencies

GnomAD3 genomes
AF:
0.000440
AC:
67
AN:
152202
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00124
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:
0.000647
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000262
AC:
60
AN:
229094
Hom.:
0
AF XY:
0.000253
AC XY:
32
AN XY:
126564
show subpopulations
Gnomad AFR exome
AF:
0.0000716
Gnomad AMR exome
AF:
0.000292
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:
0.000445
Gnomad OTH exome
AF:
0.000342
GnomAD4 exome
AF:
0.000369
AC:
443
AN:
1199820
Hom.:
0
Cov.:
30
AF XY:
0.000392
AC XY:
233
AN XY:
594982
show subpopulations
Gnomad4 AFR exome
AF:
0.0000380
Gnomad4 AMR exome
AF:
0.000295
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000240
Gnomad4 FIN exome
AF:
0.0000581
Gnomad4 NFE exome
AF:
0.000430
Gnomad4 OTH exome
AF:
0.000364
GnomAD4 genome
AF:
0.000440
AC:
67
AN:
152202
Hom.:
0
Cov.:
32
AF XY:
0.000417
AC XY:
31
AN XY:
74358
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.00124
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000647
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.000427
Hom.:
0
Bravo
AF:
0.000601
TwinsUK
AF:
0.000539
AC:
2
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000251
AC:
1
ExAC
AF:
0.000208
AC:
24
EpiCase
AF:
0.000709
EpiControl
AF:
0.000534

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

RARB-related disorder Uncertain:1
Uncertain significance, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesMar 24, 2024The RARB c.20C>T variant is predicted to result in the amino acid substitution p.Ala7Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.045% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.17
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.080
T
Eigen
Benign
0.12
Eigen_PC
Uncertain
0.29
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.53
T
M_CAP
Benign
0.056
D
MetaRNN
Benign
0.14
T
MetaSVM
Uncertain
-0.17
T
MutationTaster
Benign
0.92
N
PROVEAN
Benign
-0.34
N
REVEL
Uncertain
0.39
Sift
Benign
0.031
D
Sift4G
Benign
0.79
T
MVP
0.54
ClinPred
0.033
T
GERP RS
5.9

Splicing

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: rs370145541; hg19: chr3-25215908; API