rs1153604

Variant summary

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

The NM_000965.5(RARB):​c.448+30513G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 151,912 control chromosomes in the GnomAD database, including 22,188 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 0.50 ( 22188 hom., cov: 31)

Consequence

RARB
NM_000965.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.66
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 Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.02).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RARBNM_000965.5 linkuse as main transcriptc.448+30513G>A intron_variant ENST00000330688.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RARBENST00000330688.9 linkuse as main transcriptc.448+30513G>A intron_variant 1 NM_000965.5 P1P10826-2

Frequencies

GnomAD3 genomes
AF:
0.495
AC:
75161
AN:
151796
Hom.:
22130
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.833
Gnomad AMI
AF:
0.269
Gnomad AMR
AF:
0.466
Gnomad ASJ
AF:
0.384
Gnomad EAS
AF:
0.495
Gnomad SAS
AF:
0.305
Gnomad FIN
AF:
0.338
Gnomad MID
AF:
0.446
Gnomad NFE
AF:
0.344
Gnomad OTH
AF:
0.443
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.496
AC:
75280
AN:
151912
Hom.:
22188
Cov.:
31
AF XY:
0.490
AC XY:
36353
AN XY:
74228
show subpopulations
Gnomad4 AFR
AF:
0.834
Gnomad4 AMR
AF:
0.466
Gnomad4 ASJ
AF:
0.384
Gnomad4 EAS
AF:
0.494
Gnomad4 SAS
AF:
0.305
Gnomad4 FIN
AF:
0.338
Gnomad4 NFE
AF:
0.344
Gnomad4 OTH
AF:
0.448
Alfa
AF:
0.413
Hom.:
3092
Bravo
AF:
0.526
Asia WGS
AF:
0.436
AC:
1517
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
0.0090
DANN
Benign
0.48

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.

Other links and lift over

dbSNP: rs1153604; hg19: chr3-25573327; API