chr3-25501097-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000965.5(RARB):​c.307-85A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00652 in 1,450,442 control chromosomes in the GnomAD database, including 499 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.034 ( 282 hom., cov: 32)
Exomes 𝑓: 0.0033 ( 217 hom. )

Consequence

RARB
NM_000965.5 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.502
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 -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 3-25501097-A-G is Benign according to our data. Variant chr3-25501097-A-G is described in ClinVar as [Benign]. Clinvar id is 1265767.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RARBNM_000965.5 linkuse as main transcriptc.307-85A>G intron_variant ENST00000330688.9 NP_000956.2
LOC124909356XR_007095847.1 linkuse as main transcriptn.1090T>C non_coding_transcript_exon_variant 2/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RARBENST00000330688.9 linkuse as main transcriptc.307-85A>G intron_variant 1 NM_000965.5 ENSP00000332296 P1P10826-2

Frequencies

GnomAD3 genomes
AF:
0.0338
AC:
5142
AN:
152150
Hom.:
278
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.115
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0191
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000621
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000559
Gnomad OTH
AF:
0.0254
GnomAD4 exome
AF:
0.00331
AC:
4300
AN:
1298174
Hom.:
217
AF XY:
0.00293
AC XY:
1874
AN XY:
640166
show subpopulations
Gnomad4 AFR exome
AF:
0.122
Gnomad4 AMR exome
AF:
0.00925
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000189
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000275
Gnomad4 OTH exome
AF:
0.00804
GnomAD4 genome
AF:
0.0339
AC:
5164
AN:
152268
Hom.:
282
Cov.:
32
AF XY:
0.0330
AC XY:
2454
AN XY:
74452
show subpopulations
Gnomad4 AFR
AF:
0.115
Gnomad4 AMR
AF:
0.0191
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000622
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000544
Gnomad4 OTH
AF:
0.0251
Alfa
AF:
0.0157
Hom.:
21
Bravo
AF:
0.0390
Asia WGS
AF:
0.00693
AC:
24
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxMay 14, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
0.88
DANN
Benign
0.35

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: rs7623934; hg19: chr3-25542588; API