chr3-25461378-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000965.5(RARB):​c.306+37T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,604,214 control chromosomes in the GnomAD database, including 11,144 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1374 hom., cov: 32)
Exomes 𝑓: 0.11 ( 9770 hom. )

Consequence

RARB
NM_000965.5 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.210
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 -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 3-25461378-T-G is Benign according to our data. Variant chr3-25461378-T-G is described in ClinVar as [Benign]. Clinvar id is 1277051.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RARBNM_000965.5 linkuse as main transcriptc.306+37T>G intron_variant ENST00000330688.9 NP_000956.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RARBENST00000330688.9 linkuse as main transcriptc.306+37T>G intron_variant 1 NM_000965.5 ENSP00000332296 P1P10826-2

Frequencies

GnomAD3 genomes
AF:
0.130
AC:
19819
AN:
152082
Hom.:
1371
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.182
Gnomad AMI
AF:
0.0252
Gnomad AMR
AF:
0.0927
Gnomad ASJ
AF:
0.0853
Gnomad EAS
AF:
0.117
Gnomad SAS
AF:
0.140
Gnomad FIN
AF:
0.137
Gnomad MID
AF:
0.139
Gnomad NFE
AF:
0.110
Gnomad OTH
AF:
0.127
GnomAD3 exomes
AF:
0.114
AC:
27616
AN:
242730
Hom.:
1804
AF XY:
0.114
AC XY:
14942
AN XY:
130914
show subpopulations
Gnomad AFR exome
AF:
0.191
Gnomad AMR exome
AF:
0.0640
Gnomad ASJ exome
AF:
0.0930
Gnomad EAS exome
AF:
0.0982
Gnomad SAS exome
AF:
0.139
Gnomad FIN exome
AF:
0.133
Gnomad NFE exome
AF:
0.112
Gnomad OTH exome
AF:
0.112
GnomAD4 exome
AF:
0.113
AC:
164127
AN:
1452012
Hom.:
9770
Cov.:
32
AF XY:
0.113
AC XY:
81813
AN XY:
721544
show subpopulations
Gnomad4 AFR exome
AF:
0.188
Gnomad4 AMR exome
AF:
0.0663
Gnomad4 ASJ exome
AF:
0.0891
Gnomad4 EAS exome
AF:
0.131
Gnomad4 SAS exome
AF:
0.132
Gnomad4 FIN exome
AF:
0.129
Gnomad4 NFE exome
AF:
0.110
Gnomad4 OTH exome
AF:
0.116
GnomAD4 genome
AF:
0.130
AC:
19848
AN:
152202
Hom.:
1374
Cov.:
32
AF XY:
0.132
AC XY:
9798
AN XY:
74404
show subpopulations
Gnomad4 AFR
AF:
0.182
Gnomad4 AMR
AF:
0.0928
Gnomad4 ASJ
AF:
0.0853
Gnomad4 EAS
AF:
0.118
Gnomad4 SAS
AF:
0.139
Gnomad4 FIN
AF:
0.137
Gnomad4 NFE
AF:
0.110
Gnomad4 OTH
AF:
0.126
Alfa
AF:
0.129
Hom.:
246
Bravo
AF:
0.129
Asia WGS
AF:
0.145
AC:
502
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingGeneDxMay 15, 2021- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
0.71
DANN
Benign
0.41

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: rs2067964; hg19: chr3-25502869; API