rs922939

chr3-25423517-C-Achr3-25423517-C-Gchr3-25423517-C-T

Variant summary

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

The NM_001290216.3(RARB):c.179-37676C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 152,048 control chromosomes in the GnomAD database, including 31,414 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 0.64 (31414 hom., cov: 32)
• Consequence: RARB NM_001290216.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.435

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RARB	NM_001290216.3	c.179-37676C>A		intron_variant
RARB	NM_001290300.2	c.29-37676C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RARB	ENST00000383772.9	c.179-37676C>A		intron_variant		5
RARB	ENST00000455576.2	c.179-37676C>A		intron_variant		4
RARB	ENST00000686715.1	c.179-37676C>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97233 AN: 151930 Hom.: 31404 Cov.: 32

Gnomad AFR AF: 0.549

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.797

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.629

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

GnomAD4 genome AF: 0.640 AC: 97280 AN: 152048 Hom.: 31414 Cov.: 32 AF XY: 0.642 AC XY: 47718 AN XY: 74288

Gnomad4 AFR AF: 0.549

Gnomad4 AMR AF: 0.659

Gnomad4 ASJ AF: 0.663

Gnomad4 EAS AF: 0.797

Gnomad4 SAS AF: 0.689

Gnomad4 FIN AF: 0.688

Gnomad4 NFE AF: 0.666

Gnomad4 OTH AF: 0.628

Alfa AF: 0.656 Hom.: 40194

Bravo AF: 0.633

Asia WGS AF: 0.713 AC: 2474 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.42
Dann	Benign	0.22

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs922939; hg19: chr3-25465008;