rs322668

Positions:

• chr3-25302124-G-A
• chr3-25302124-G-C
• chr3-25302124-G-T

Variant summary

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

The NM_001290216.3(RARB):​c.178+127549G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 152,154 control chromosomes in the GnomAD database, including 42,573 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 0.74 (42573 hom., cov: 33)
• Consequence: RARB NM_001290216.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.213

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RARB	NM_001290216.3	c.178+127549G>A		intron_variant			NP_001277145.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RARB	ENST00000383772.9	c.178+127549G>A		intron_variant		5		ENSP00000373282.5
RARB	ENST00000686715.1	c.178+127549G>A		intron_variant				ENSP00000510539.1
RARB	ENST00000687353.1	c.178+127549G>A		intron_variant				ENSP00000508588.1

Frequencies

GnomAD3 genomes AF: 0.743 AC: 113025 AN: 152036 Hom.: 42530 Cov.: 33

Gnomad AFR AF: 0.783

Gnomad AMI AF: 0.696

Gnomad AMR AF: 0.809

Gnomad ASJ AF: 0.711

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.870

Gnomad FIN AF: 0.681

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.688

Gnomad OTH AF: 0.753

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

GnomAD4 genome AF: 0.744 AC: 113128 AN: 152154 Hom.: 42573 Cov.: 33 AF XY: 0.746 AC XY: 55481 AN XY: 74384

Gnomad4 AFR AF: 0.783

Gnomad4 AMR AF: 0.810

Gnomad4 ASJ AF: 0.711

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.870

Gnomad4 FIN AF: 0.681

Gnomad4 NFE AF: 0.688

Gnomad4 OTH AF: 0.757

Alfa AF: 0.717 Hom.: 31047

Bravo AF: 0.754

Asia WGS AF: 0.926 AC: 3220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.31
DANN	Benign	0.64

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs322668; hg19: chr3-25343615;