rs1286654

chr3-25489774-C-A

Variant summary

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

The NM_000965.5(RARB):c.307-11408C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 152,112 control chromosomes in the GnomAD database, including 6,367 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 0.28 (6367 hom., cov: 34)
• Consequence: RARB NM_000965.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0620

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RARB	NM_000965.5	c.307-11408C>A		intron_variant		ENST00000330688.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RARB	ENST00000330688.9	c.307-11408C>A		intron_variant		1	NM_000965.5	P1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43274 AN: 151994 Hom.: 6357 Cov.: 34

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.303

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

GnomAD4 genome AF: 0.285 AC: 43315 AN: 152112 Hom.: 6367 Cov.: 34 AF XY: 0.288 AC XY: 21419 AN XY: 74354

Gnomad4 AFR AF: 0.255

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.305

Gnomad4 EAS AF: 0.453

Gnomad4 SAS AF: 0.267

Gnomad4 FIN AF: 0.313

Gnomad4 NFE AF: 0.271

Gnomad4 OTH AF: 0.308

Alfa AF: 0.280 Hom.: 7365

Bravo AF: 0.290

Asia WGS AF: 0.367 AC: 1272 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	2.8
Dann	Benign	0.73

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: rs1286654; hg19: chr3-25531265;