rs6550978

chr3-25449478-G-Achr3-25449478-G-C

Variant summary

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

The NM_000965.5(RARB):c.158-11715G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.682 in 151,778 control chromosomes in the GnomAD database, including 35,965 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 0.68 (35965 hom., cov: 31)
• Consequence: RARB NM_000965.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.615

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=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RARB	NM_000965.5	c.158-11715G>A		intron_variant		ENST00000330688.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RARB	ENST00000330688.9	c.158-11715G>A		intron_variant		1	NM_000965.5	P1

Frequencies

GnomAD3 genomes AF: 0.682 AC: 103383 AN: 151658 Hom.: 35937 Cov.: 31

Gnomad AFR AF: 0.812

Gnomad AMI AF: 0.838

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.827

Gnomad SAS AF: 0.659

Gnomad FIN AF: 0.645

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.693

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

GnomAD4 genome AF: 0.682 AC: 103469 AN: 151778 Hom.: 35965 Cov.: 31 AF XY: 0.683 AC XY: 50673 AN XY: 74144

Gnomad4 AFR AF: 0.812

Gnomad4 AMR AF: 0.612

Gnomad4 ASJ AF: 0.641

Gnomad4 EAS AF: 0.828

Gnomad4 SAS AF: 0.658

Gnomad4 FIN AF: 0.645

Gnomad4 NFE AF: 0.614

Gnomad4 OTH AF: 0.692

Alfa AF: 0.631 Hom.: 20358

Bravo AF: 0.686

Asia WGS AF: 0.721 AC: 2506 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	8.3
Dann	Benign	0.85

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: rs6550978; hg19: chr3-25490969;