rs6780105

Positions:

• chr3-25262214-C-G

Variant summary

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

The NM_001290216.3(RARB):​c.178+87639C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,160 control chromosomes in the GnomAD database, including 1,127 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 0.11 (1127 hom., cov: 32)
• Consequence: RARB NM_001290216.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0380

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RARB	NM_001290216.3	c.178+87639C>G		intron_variant			NP_001277145.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RARB	ENST00000383772.9	c.178+87639C>G		intron_variant		5		ENSP00000373282
RARB	ENST00000455576.2	c.178+87639C>G		intron_variant		4		ENSP00000508527
RARB	ENST00000686715.1	c.178+87639C>G		intron_variant				ENSP00000510539

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16348 AN: 152042 Hom.: 1127 Cov.: 32

Gnomad AFR AF: 0.0308

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.0858

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0420

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.107 AC: 16344 AN: 152160 Hom.: 1127 Cov.: 32 AF XY: 0.104 AC XY: 7702 AN XY: 74368

Gnomad4 AFR AF: 0.0307

Gnomad4 AMR AF: 0.0857

Gnomad4 ASJ AF: 0.104

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.0421

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.109

Alfa AF: 0.137 Hom.: 199

Bravo AF: 0.0985

Asia WGS AF: 0.0250 AC: 88 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.0
DANN	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6780105; hg19: chr3-25303705;