dbSNP rs1286756: RARB:c.448+24266G>A (chr3-25525589-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_000965.5(RARB):c.448+24266G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 152,076 control chromosomes in the GnomAD database, including 25,593 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 0.55 ( 25593 hom., cov: 32)

Consequence

RARB
NM_000965.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.242

Publications

6 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

RARB links:

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=-0.97).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RARB	NM_000965.5 link	c.448+24266G>A		intron_variant	Intron 3 of 7	ENST00000330688.9	NP_000956.2	P10826-2F1D8S6Q86UC5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RARB	ENST00000330688.9 link	c.448+24266G>A		intron_variant	Intron 3 of 7	1	NM_000965.5	ENSP00000332296.4		P10826-2

Frequencies

GnomAD3 genomes

AF:

0.547

AC:

83169

AN:

151958

Hom.:

25533

Cov.:

show subpopulations

Gnomad AFR

AF:

0.834

Gnomad AMI

AF:

0.277

Gnomad AMR

AF:

0.610

Gnomad ASJ

AF:

0.453

Gnomad EAS

AF:

0.532

Gnomad SAS

AF:

0.334

Gnomad FIN

AF:

0.399

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.408

Gnomad OTH

AF:

0.516

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.548

AC:

83288

AN:

152076

Hom.:

25593

Cov.:

AF XY:

0.544

AC XY:

40420

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.834

AC:

34629

AN:

41524

American (AMR)

AF:

0.611

AC:

9329

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.453

AC:

1571

AN:

3466

East Asian (EAS)

AF:

0.531

AC:

2745

AN:

5172

South Asian (SAS)

AF:

0.333

AC:

1605

AN:

4820

European-Finnish (FIN)

AF:

0.399

AC:

4207

AN:

10552

Middle Eastern (MID)

AF:

0.497

AC:

146

AN:

294

European-Non Finnish (NFE)

AF:

0.408

AC:

27708

AN:

67952

Other (OTH)

AF:

0.519

AC:

1096

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1685

3370

5055

6740

8425

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.447

Hom.:

12023

Bravo

AF:

0.584

Asia WGS

AF:

0.468

AC:

1626

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.71

(source)

DANN

Benign

0.24

PhyloP100

-0.24

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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rs1286756

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over