chr3-25418006-T-C

Position:

• chr3-25418006-T-C

Variant summary

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

The NM_001290216.3(RARB):​c.179-43187T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 152,070 control chromosomes in the GnomAD database, including 33,415 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 0.65 (33415 hom., cov: 31)
• Consequence: RARB NM_001290216.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0600

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RARB	NM_001290216.3	c.179-43187T>C		intron_variant			NP_001277145.1
RARB	NM_001290300.2	c.29-43187T>C		intron_variant			NP_001277229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RARB	ENST00000383772.9	c.179-43187T>C		intron_variant		5		ENSP00000373282
RARB	ENST00000455576.2	c.179-43187T>C		intron_variant		4		ENSP00000508527
RARB	ENST00000686715.1	c.179-43187T>C		intron_variant				ENSP00000510539

Frequencies

GnomAD3 genomes AF: 0.654 AC: 99309 AN: 151950 Hom.: 33388 Cov.: 31

Gnomad AFR AF: 0.798

Gnomad AMI AF: 0.728

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.823

Gnomad SAS AF: 0.691

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.654

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

GnomAD4 genome AF: 0.654 AC: 99387 AN: 152070 Hom.: 33415 Cov.: 31 AF XY: 0.647 AC XY: 48066 AN XY: 74316

Gnomad4 AFR AF: 0.797

Gnomad4 AMR AF: 0.570

Gnomad4 ASJ AF: 0.610

Gnomad4 EAS AF: 0.823

Gnomad4 SAS AF: 0.690

Gnomad4 FIN AF: 0.487

Gnomad4 NFE AF: 0.596

Gnomad4 OTH AF: 0.654

Alfa AF: 0.614 Hom.: 3438

Bravo AF: 0.664

Asia WGS AF: 0.738 AC: 2569 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.7
DANN	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7648325; hg19: chr3-25459497;