3-25483077-A-G

Variant summary

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

The NM_000965.5(RARB):​c.307-18105A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 152,026 control chromosomes in the GnomAD database, including 20,286 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 0.49 ( 20286 hom., cov: 32)

Consequence

RARB
NM_000965.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.971
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=-0.87).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RARBNM_000965.5 linkuse as main transcriptc.307-18105A>G intron_variant ENST00000330688.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RARBENST00000330688.9 linkuse as main transcriptc.307-18105A>G intron_variant 1 NM_000965.5 P1P10826-2

Frequencies

GnomAD3 genomes
AF:
0.493
AC:
74923
AN:
151908
Hom.:
20269
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.263
Gnomad AMI
AF:
0.758
Gnomad AMR
AF:
0.487
Gnomad ASJ
AF:
0.576
Gnomad EAS
AF:
0.427
Gnomad SAS
AF:
0.650
Gnomad FIN
AF:
0.583
Gnomad MID
AF:
0.519
Gnomad NFE
AF:
0.607
Gnomad OTH
AF:
0.490
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.493
AC:
74959
AN:
152026
Hom.:
20286
Cov.:
32
AF XY:
0.494
AC XY:
36739
AN XY:
74298
show subpopulations
Gnomad4 AFR
AF:
0.263
Gnomad4 AMR
AF:
0.487
Gnomad4 ASJ
AF:
0.576
Gnomad4 EAS
AF:
0.427
Gnomad4 SAS
AF:
0.651
Gnomad4 FIN
AF:
0.583
Gnomad4 NFE
AF:
0.607
Gnomad4 OTH
AF:
0.493
Alfa
AF:
0.565
Hom.:
5063
Bravo
AF:
0.471
Asia WGS
AF:
0.495
AC:
1723
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
0.062
DANN
Benign
0.49

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: rs6550982; hg19: chr3-25524568; API