3-25528074-C-T

Variant names:

• chr3-25528074-C-T
• rs1153600
• NM_000965.5:c.448+26751C>T

Variant summary

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

The NM_000965.5(RARB):​c.448+26751C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 151,984 control chromosomes in the GnomAD database, including 18,880 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 (18880 hom., cov: 32)
• Consequence: RARB NM_000965.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.932

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=-0.56).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RARB	NM_000965.5	c.448+26751C>T		intron_variant	Intron 3 of 7	ENST00000330688.9	NP_000956.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RARB	ENST00000330688.9	c.448+26751C>T		intron_variant	Intron 3 of 7	1	NM_000965.5	ENSP00000332296.4

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70134 AN: 151868 Hom.: 18828 Cov.: 32

Gnomad AFR AF: 0.732

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.502

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.424

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

GnomAD4 genome AF: 0.462 AC: 70248 AN: 151984 Hom.: 18880 Cov.: 32 AF XY: 0.460 AC XY: 34148 AN XY: 74268

Gnomad4 AFR AF: 0.732

Gnomad4 AMR AF: 0.542

Gnomad4 ASJ AF: 0.350

Gnomad4 EAS AF: 0.501

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.333

Gnomad4 NFE AF: 0.319

Gnomad4 OTH AF: 0.429

Alfa AF: 0.327 Hom.: 1232

Bravo AF: 0.498

Asia WGS AF: 0.429 AC: 1491 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	17
DANN	Benign	0.78

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: rs1153600; hg19: chr3-25569565;