3-25572957-G-A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000965.5(RARB):​c.609+3039G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,024 control chromosomes in the GnomAD database, including 2,666 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 0.19 ( 2666 hom., cov: 32)

Consequence

RARB
NM_000965.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.956

Publications

5 publications found
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]
RARB Gene-Disease associations (from GenCC):
  • microphthalmia, syndromic 12
    Inheritance: AR, AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen, Baylor College of Medicine Research Center
  • Matthew-Wood syndrome
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RARBNM_000965.5 linkc.609+3039G>A intron_variant Intron 4 of 7 ENST00000330688.9 NP_000956.2 P10826-2F1D8S6Q86UC5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RARBENST00000330688.9 linkc.609+3039G>A intron_variant Intron 4 of 7 1 NM_000965.5 ENSP00000332296.4 P10826-2

Frequencies

GnomAD3 genomes
AF:
0.188
AC:
28614
AN:
151906
Hom.:
2667
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.169
Gnomad AMI
AF:
0.188
Gnomad AMR
AF:
0.161
Gnomad ASJ
AF:
0.203
Gnomad EAS
AF:
0.258
Gnomad SAS
AF:
0.155
Gnomad FIN
AF:
0.196
Gnomad MID
AF:
0.153
Gnomad NFE
AF:
0.202
Gnomad OTH
AF:
0.180
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.188
AC:
28620
AN:
152024
Hom.:
2666
Cov.:
32
AF XY:
0.188
AC XY:
13938
AN XY:
74324
show subpopulations
African (AFR)
AF:
0.169
AC:
7007
AN:
41460
American (AMR)
AF:
0.161
AC:
2456
AN:
15278
Ashkenazi Jewish (ASJ)
AF:
0.203
AC:
703
AN:
3470
East Asian (EAS)
AF:
0.259
AC:
1334
AN:
5158
South Asian (SAS)
AF:
0.154
AC:
743
AN:
4816
European-Finnish (FIN)
AF:
0.196
AC:
2069
AN:
10582
Middle Eastern (MID)
AF:
0.164
AC:
48
AN:
292
European-Non Finnish (NFE)
AF:
0.202
AC:
13716
AN:
67950
Other (OTH)
AF:
0.177
AC:
373
AN:
2106
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
1185
2370
3554
4739
5924
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
324
648
972
1296
1620
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.193
Hom.:
2210
Bravo
AF:
0.185
Asia WGS
AF:
0.204
AC:
712
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
0.10
DANN
Benign
0.64
PhyloP100
-0.96
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs12635379; hg19: chr3-25614448; API