rs2164360

Positions:

• chr3-25591403-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.787-2100C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,052 control chromosomes in the GnomAD database, including 2,516 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 0.18 (2516 hom., cov: 33)
• Consequence: RARB NM_000965.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.211

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 (AMR) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RARB	NM_000965.5	c.787-2100C>T		intron_variant		ENST00000330688.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RARB	ENST00000330688.9	c.787-2100C>T		intron_variant		1	NM_000965.5	P1

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26893 AN: 151934 Hom.: 2511 Cov.: 33

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.177 AC: 26914 AN: 152052 Hom.: 2516 Cov.: 33 AF XY: 0.178 AC XY: 13211 AN XY: 74328

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.170

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.159

Alfa AF: 0.198 Hom.: 4591

Bravo AF: 0.174

Asia WGS AF: 0.171 AC: 593 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.71

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: rs2164360; hg19: chr3-25632894;