rs1153584

chr3-25502627-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.448+1304G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 152,074 control chromosomes in the GnomAD database, including 20,699 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 0.51 (20699 hom., cov: 32)
• Consequence: RARB NM_000965.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.907

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]

LOC124909356 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RARB	NM_000965.5	c.448+1304G>A		intron_variant		ENST00000330688.9
LOC124909356	XR_007095847.1	n.517-957C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RARB	ENST00000330688.9	c.448+1304G>A		intron_variant		1	NM_000965.5	P1

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77126 AN: 151956 Hom.: 20670 Cov.: 32

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.509

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

GnomAD4 genome AF: 0.508 AC: 77211 AN: 152074 Hom.: 20699 Cov.: 32 AF XY: 0.505 AC XY: 37574 AN XY: 74346

Gnomad4 AFR AF: 0.681

Gnomad4 AMR AF: 0.515

Gnomad4 ASJ AF: 0.469

Gnomad4 EAS AF: 0.570

Gnomad4 SAS AF: 0.375

Gnomad4 FIN AF: 0.441

Gnomad4 NFE AF: 0.421

Gnomad4 OTH AF: 0.511

Alfa AF: 0.444 Hom.: 9080

Bravo AF: 0.526

Asia WGS AF: 0.515 AC: 1791 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	0.13
Dann	Benign	0.70

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: rs1153584; hg19: chr3-25544118;