rs1368265

Positions:

• chr3-25500079-A-G

Variant summary

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

The NM_000965.5(RARB):​c.307-1103A>G 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 152,090 control chromosomes in the GnomAD database, including 20,703 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 (20703 hom., cov: 33)
• Consequence: RARB NM_000965.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.442

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RARB	NM_000965.5	c.307-1103A>G		intron_variant		ENST00000330688.9	NP_000956.2
LOC124909356	XR_007095847.1	n.2108T>C		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RARB	ENST00000330688.9	c.307-1103A>G		intron_variant		1	NM_000965.5	ENSP00000332296	P1

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77163 AN: 151972 Hom.: 20675 Cov.: 33

Gnomad AFR AF: 0.682

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.547

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.505

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

GnomAD4 genome AF: 0.508 AC: 77246 AN: 152090 Hom.: 20703 Cov.: 33 AF XY: 0.505 AC XY: 37565 AN XY: 74374

Gnomad4 AFR AF: 0.682

Gnomad4 AMR AF: 0.516

Gnomad4 ASJ AF: 0.469

Gnomad4 EAS AF: 0.546

Gnomad4 SAS AF: 0.360

Gnomad4 FIN AF: 0.441

Gnomad4 NFE AF: 0.423

Gnomad4 OTH AF: 0.508

Alfa AF: 0.474 Hom.: 6194

Bravo AF: 0.526

Asia WGS AF: 0.491 AC: 1707 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.6
DANN	Benign	0.26

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: rs1368265; hg19: chr3-25541570;