rs1483856

chr3-25432454-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000965.5(RARB):c.157+3566G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.896 in 152,232 control chromosomes in the GnomAD database, including 61,200 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 0.90 (61200 hom., cov: 32)
• Consequence: RARB NM_000965.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.315

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RARB	NM_000965.5	c.157+3566G>T		intron_variant		ENST00000330688.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RARB	ENST00000330688.9	c.157+3566G>T		intron_variant		1	NM_000965.5	P1

Frequencies

GnomAD3 genomes AF: 0.896 AC: 136355 AN: 152114 Hom.: 61157 Cov.: 32

Gnomad AFR AF: 0.895

Gnomad AMI AF: 0.976

Gnomad AMR AF: 0.914

Gnomad ASJ AF: 0.905

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.926

Gnomad FIN AF: 0.860

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.889

Gnomad OTH AF: 0.869

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

GnomAD4 genome AF: 0.896 AC: 136455 AN: 152232 Hom.: 61200 Cov.: 32 AF XY: 0.897 AC XY: 66745 AN XY: 74436

Gnomad4 AFR AF: 0.895

Gnomad4 AMR AF: 0.914

Gnomad4 ASJ AF: 0.905

Gnomad4 EAS AF: 0.995

Gnomad4 SAS AF: 0.926

Gnomad4 FIN AF: 0.860

Gnomad4 NFE AF: 0.889

Gnomad4 OTH AF: 0.871

Alfa AF: 0.897 Hom.: 9905

Bravo AF: 0.899

Asia WGS AF: 0.960 AC: 3335 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.0
Dann	Benign	0.50

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

Other links and lift over

dbSNP: rs1483856; hg19: chr3-25473945;