rs7629902

chr3-25459390-G-A

Variant summary

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

The NM_000965.5(RARB):c.158-1803G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,224 control chromosomes in the GnomAD database, including 1,702 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 0.14 (1702 hom., cov: 32)
• Consequence: RARB NM_000965.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0350

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 (AFR) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RARB	NM_000965.5	c.158-1803G>A		intron_variant		ENST00000330688.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RARB	ENST00000330688.9	c.158-1803G>A		intron_variant		1	NM_000965.5	P1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21667 AN: 152106 Hom.: 1700 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.0971

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.142 AC: 21685 AN: 152224 Hom.: 1702 Cov.: 32 AF XY: 0.139 AC XY: 10359 AN XY: 74428

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.0970

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.129

Alfa AF: 0.138 Hom.: 1903

Bravo AF: 0.141

Asia WGS AF: 0.0520 AC: 182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.3
Dann	Benign	0.44

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: rs7629902; hg19: chr3-25500881;