dbSNP rs11271404: RARB:c.306+6163_306+6201delACAATCATAGCAAGCCAACGCCACTTATCCAGTGAACCA (chr3-25467503-TACAATCATAGCAAGCCAACGCCACTTATCCAGTGAACCA-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000965.5(RARB):c.306+6163_306+6201delACAATCATAGCAAGCCAACGCCACTTATCCAGTGAACCA variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.46 ( 16476 hom., cov: 0)

Consequence

RARB
NM_000965.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00

Publications

0 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 -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000965.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RARB	NM_000965.5	MANE Select	c.306+6163_306+6201delACAATCATAGCAAGCCAACGCCACTTATCCAGTGAACCA	intron	N/A	NP_000956.2
RARB	NM_001290216.3		c.327+6163_327+6201delACAATCATAGCAAGCCAACGCCACTTATCCAGTGAACCA	intron	N/A	NP_001277145.1
RARB	NM_001290300.2		c.177+6163_177+6201delACAATCATAGCAAGCCAACGCCACTTATCCAGTGAACCA	intron	N/A	NP_001277229.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RARB	ENST00000330688.9	TSL:1 MANE Select	c.306+6163_306+6201delACAATCATAGCAAGCCAACGCCACTTATCCAGTGAACCA	intron	N/A	ENSP00000332296.4
RARB	ENST00000437042.7	TSL:1	c.-31+6163_-31+6201delACAATCATAGCAAGCCAACGCCACTTATCCAGTGAACCA	intron	N/A	ENSP00000398840.2
RARB	ENST00000458646.2	TSL:1	c.-31+6163_-31+6201delACAATCATAGCAAGCCAACGCCACTTATCCAGTGAACCA	intron	N/A	ENSP00000391391.1

Frequencies

GnomAD3 genomes

AF:

0.465

AC:

70210

AN:

151138

Hom.:

16460

Cov.:

show subpopulations

Gnomad AFR

AF:

0.443

Gnomad AMI

AF:

0.512

Gnomad AMR

AF:

0.482

Gnomad ASJ

AF:

0.387

Gnomad EAS

AF:

0.669

Gnomad SAS

AF:

0.528

Gnomad FIN

AF:

0.435

Gnomad MID

AF:

0.442

Gnomad NFE

AF:

0.463

Gnomad OTH

AF:

0.445

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

GnomAD4 genome

AF:

0.465

AC:

70269

AN:

151250

Hom.:

16476

Cov.:

AF XY:

0.467

AC XY:

34478

AN XY:

73862

show subpopulations

African (AFR)

AF:

0.443

AC:

18276

AN:

41248

American (AMR)

AF:

0.482

AC:

7332

AN:

15212

Ashkenazi Jewish (ASJ)

AF:

0.387

AC:

1341

AN:

3462

East Asian (EAS)

AF:

0.670

AC:

3380

AN:

5046

South Asian (SAS)

AF:

0.527

AC:

2523

AN:

4792

European-Finnish (FIN)

AF:

0.435

AC:

4554

AN:

10474

Middle Eastern (MID)

AF:

0.451

AC:

129

AN:

286

European-Non Finnish (NFE)

AF:

0.463

AC:

31333

AN:

67736

Other (OTH)

AF:

0.449

AC:

939

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.427

Heterozygous variant carriers

1961

3922

5883

7844

9805

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

650

1300

1950

2600

3250

<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:

0.468

Hom.:

1784

Asia WGS

AF:

0.581

AC:

2019

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.0

Mutation Taster

=27/73

disease causing (long InDel)

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over