chr3-25461305-G-A
Position:
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_000965.5(RARB):c.270G>A(p.Gly90=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00044 in 1,613,848 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.00059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00042 ( 11 hom. )
Consequence
RARB
NM_000965.5 synonymous
NM_000965.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0250
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 -15 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP6
Variant 3-25461305-G-A is Benign according to our data. Variant chr3-25461305-G-A is described in ClinVar as [Benign]. Clinvar id is 772966.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.025 with no splicing effect.
BS2
High Homozygotes in GnomAdExome4 at 11 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RARB | NM_000965.5 | c.270G>A | p.Gly90= | synonymous_variant | 2/8 | ENST00000330688.9 | NP_000956.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RARB | ENST00000330688.9 | c.270G>A | p.Gly90= | synonymous_variant | 2/8 | 1 | NM_000965.5 | ENSP00000332296 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000586 AC: 89AN: 151876Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
89
AN:
151876
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00162 AC: 407AN: 251232Hom.: 4 AF XY: 0.00168 AC XY: 228AN XY: 135742
GnomAD3 exomes
AF:
AC:
407
AN:
251232
Hom.:
AF XY:
AC XY:
228
AN XY:
135742
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000425 AC: 621AN: 1461854Hom.: 11 Cov.: 31 AF XY: 0.000474 AC XY: 345AN XY: 727224
GnomAD4 exome
AF:
AC:
621
AN:
1461854
Hom.:
Cov.:
31
AF XY:
AC XY:
345
AN XY:
727224
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.000586 AC: 89AN: 151994Hom.: 0 Cov.: 32 AF XY: 0.000687 AC XY: 51AN XY: 74280
GnomAD4 genome
AF:
AC:
89
AN:
151994
Hom.:
Cov.:
32
AF XY:
AC XY:
51
AN XY:
74280
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
10
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Microphthalmia, syndromic 12 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 27, 2023 | - - |
RARB-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 16, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at