rs9840225

chr3-25139539-G-A

Variant summary

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

The NM_001290216.3(RARB):c.-279-34580G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,060 control chromosomes in the GnomAD database, including 976 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 (976 hom., cov: 33)
• Consequence: RARB NM_001290216.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.843

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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RARB	NM_001290216.3	c.-279-34580G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RARB	ENST00000383772.9	c.-280+7331G>A		intron_variant		5
RARB	ENST00000455576.2	c.-279-34580G>A		intron_variant		4
RARB	ENST00000686715.1	c.-279-34580G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16902 AN: 151942 Hom.: 971 Cov.: 33

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.0771

Gnomad ASJ AF: 0.0734

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0665

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.111 AC: 16918 AN: 152060 Hom.: 976 Cov.: 33 AF XY: 0.109 AC XY: 8069 AN XY: 74322

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.0770

Gnomad4 ASJ AF: 0.0734

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0662

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.103

Alfa AF: 0.120 Hom.: 139

Bravo AF: 0.107

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.20
Dann	Benign	0.21

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9840225; hg19: chr3-25181030;