rs13314219

Positions:

• chr3-25454146-C-A
• chr3-25454146-C-G
• chr3-25454146-C-T

Variant summary

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

The NM_000965.5(RARB):​c.158-7047C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 152,108 control chromosomes in the GnomAD database, including 31,520 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 0.64 (31520 hom., cov: 33)
• Consequence: RARB NM_000965.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06

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=-0.63).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RARB	NM_000965.5	c.158-7047C>A		intron_variant		ENST00000330688.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RARB	ENST00000330688.9	c.158-7047C>A		intron_variant		1	NM_000965.5	P1

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97349 AN: 151988 Hom.: 31484 Cov.: 33

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.842

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.693

Gnomad EAS AF: 0.843

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.654

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

GnomAD4 genome AF: 0.641 AC: 97436 AN: 152108 Hom.: 31520 Cov.: 33 AF XY: 0.639 AC XY: 47500 AN XY: 74356

Gnomad4 AFR AF: 0.664

Gnomad4 AMR AF: 0.599

Gnomad4 ASJ AF: 0.693

Gnomad4 EAS AF: 0.843

Gnomad4 SAS AF: 0.619

Gnomad4 FIN AF: 0.561

Gnomad4 NFE AF: 0.629

Gnomad4 OTH AF: 0.654

Alfa AF: 0.630 Hom.: 59304

Bravo AF: 0.645

Asia WGS AF: 0.713 AC: 2480 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	9.9
DANN	Benign	0.72

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: rs13314219; hg19: chr3-25495637;