3-25471277-A-T

Position:

• chr3-25471277-A-T

Variant summary

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

The ENST00000330688.9(RARB):​c.306+9936A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 151,930 control chromosomes in the GnomAD database, including 18,733 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 0.44 (18733 hom., cov: 31)
• Consequence: RARB ENST00000330688.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.625

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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RARB	NM_000965.5	c.306+9936A>T		intron_variant		ENST00000330688.9	NP_000956.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RARB	ENST00000330688.9	c.306+9936A>T		intron_variant		1	NM_000965.5	ENSP00000332296	P1

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67546 AN: 151812 Hom.: 18732 Cov.: 31

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.553

Gnomad FIN AF: 0.604

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.619

Gnomad OTH AF: 0.439

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

GnomAD4 genome AF: 0.445 AC: 67544 AN: 151930 Hom.: 18733 Cov.: 31 AF XY: 0.445 AC XY: 33048 AN XY: 74222

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.463

Gnomad4 ASJ AF: 0.469

Gnomad4 EAS AF: 0.328

Gnomad4 SAS AF: 0.554

Gnomad4 FIN AF: 0.604

Gnomad4 NFE AF: 0.619

Gnomad4 OTH AF: 0.437

Alfa AF: 0.548 Hom.: 3259

Bravo AF: 0.417

Asia WGS AF: 0.415 AC: 1444 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.9
DANN	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs871963; hg19: chr3-25512768;