3-25566022-A-C

Position:

• chr3-25566022-A-C

Variant summary

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

The NM_000965.5(RARB):​c.449-3736A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 151,890 control chromosomes in the GnomAD database, including 16,238 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 0.46 (16238 hom., cov: 31)
• Consequence: RARB NM_000965.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.71

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RARB	NM_000965.5	c.449-3736A>C		intron_variant		ENST00000330688.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RARB	ENST00000330688.9	c.449-3736A>C		intron_variant		1	NM_000965.5	P1

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69767 AN: 151772 Hom.: 16209 Cov.: 31

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.428

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

GnomAD4 genome AF: 0.460 AC: 69846 AN: 151890 Hom.: 16238 Cov.: 31 AF XY: 0.457 AC XY: 33922 AN XY: 74230

Gnomad4 AFR AF: 0.535

Gnomad4 AMR AF: 0.458

Gnomad4 ASJ AF: 0.363

Gnomad4 EAS AF: 0.474

Gnomad4 SAS AF: 0.424

Gnomad4 FIN AF: 0.426

Gnomad4 NFE AF: 0.430

Gnomad4 OTH AF: 0.428

Alfa AF: 0.448 Hom.: 2622

Bravo AF: 0.467

Asia WGS AF: 0.463 AC: 1614 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.27
DANN	Benign	0.79

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: rs1730240; hg19: chr3-25607513;