rs1368262

Positions:

• chr3-25479074-A-G
• chr3-25479074-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_000965.5(RARB):​c.306+17733A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 152,000 control chromosomes in the GnomAD database, including 7,948 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 0.29 (7948 hom., cov: 32)
• Consequence: RARB NM_000965.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.250

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RARB	NM_000965.5	c.306+17733A>G		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+17733A>G		intron_variant		1	NM_000965.5	ENSP00000332296	P1

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43396 AN: 151882 Hom.: 7930 Cov.: 32

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.258

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

GnomAD4 genome AF: 0.286 AC: 43469 AN: 152000 Hom.: 7948 Cov.: 32 AF XY: 0.283 AC XY: 21036 AN XY: 74320

Gnomad4 AFR AF: 0.528

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.221

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.184

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.261

Alfa AF: 0.227 Hom.: 1512

Bravo AF: 0.298

Asia WGS AF: 0.246 AC: 857 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	9.2
DANN	Benign	0.80

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: rs1368262; hg19: chr3-25520565;