chr3-25439187-C-T

Position:

• chr3-25439187-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.157+10299C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 151,990 control chromosomes in the GnomAD database, including 27,367 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 0.60 (27367 hom., cov: 32)
• Consequence: RARB NM_000965.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

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]

RARB (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RARB	NM_000965.5	c.157+10299C>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.157+10299C>T		intron_variant		1	NM_000965.5	ENSP00000332296.4

Frequencies

GnomAD3 genomes AF: 0.599 AC: 90975 AN: 151872 Hom.: 27360 Cov.: 32

Gnomad AFR AF: 0.547

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.644

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.771

Gnomad NFE AF: 0.618

Gnomad OTH AF: 0.658

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

GnomAD4 genome AF: 0.599 AC: 91029 AN: 151990 Hom.: 27367 Cov.: 32 AF XY: 0.597 AC XY: 44406 AN XY: 74322

Gnomad4 AFR AF: 0.547

Gnomad4 AMR AF: 0.640

Gnomad4 ASJ AF: 0.676

Gnomad4 EAS AF: 0.587

Gnomad4 SAS AF: 0.643

Gnomad4 FIN AF: 0.550

Gnomad4 NFE AF: 0.618

Gnomad4 OTH AF: 0.655

Alfa AF: 0.613 Hom.: 16162

Bravo AF: 0.604

Asia WGS AF: 0.640 AC: 2226 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.22
DANN	Benign	0.60

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: rs6550976; hg19: chr3-25480678;