dbSNP rs1153584: RARB:c.448+1304G>A (chr3-25502627-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+1304G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 152,074 control chromosomes in the GnomAD database, including 20,699 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 0.51 ( 20699 hom., cov: 32)

Consequence

RARB
NM_000965.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.907

Publications

9 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:

LOC124909356 (HGNC:):

LOC124909356 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=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RARB	NM_000965.5 link	c.448+1304G>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+1304G>A		intron_variant	Intron 3 of 7	1	NM_000965.5	ENSP00000332296.4		P10826-2

Frequencies

GnomAD3 genomes

AF:

0.508

AC:

77126

AN:

151956

Hom.:

20670

Cov.:

show subpopulations

Gnomad AFR

AF:

0.681

Gnomad AMI

AF:

0.249

Gnomad AMR

AF:

0.515

Gnomad ASJ

AF:

0.469

Gnomad EAS

AF:

0.570

Gnomad SAS

AF:

0.375

Gnomad FIN

AF:

0.441

Gnomad MID

AF:

0.494

Gnomad NFE

AF:

0.421

Gnomad OTH

AF:

0.509

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

GnomAD4 genome

AF:

0.508

AC:

77211

AN:

152074

Hom.:

20699

Cov.:

AF XY:

0.505

AC XY:

37574

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.681

AC:

28240

AN:

41464

American (AMR)

AF:

0.515

AC:

7868

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.469

AC:

1626

AN:

3470

East Asian (EAS)

AF:

0.570

AC:

2945

AN:

5168

South Asian (SAS)

AF:

0.375

AC:

1808

AN:

4822

European-Finnish (FIN)

AF:

0.441

AC:

4657

AN:

10572

Middle Eastern (MID)

AF:

0.490

AC:

143

AN:

292

European-Non Finnish (NFE)

AF:

0.421

AC:

28619

AN:

67986

Other (OTH)

AF:

0.511

AC:

1078

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1853

3706

5559

7412

9265

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

666

1332

1998

2664

3330

<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:

0.446

Hom.:

10048

Bravo

AF:

0.526

Asia WGS

AF:

0.515

AC:

1791

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.13

(source)

DANN

Benign

0.70

PhyloP100

-0.91

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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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