rs6778350

Positions:

• chr3-25465539-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.306+4198A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.876 in 152,262 control chromosomes in the GnomAD database, including 58,700 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 0.88 (58700 hom., cov: 32)
• Consequence: RARB NM_000965.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.75

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RARB	NM_000965.5	c.306+4198A>G		intron_variant		ENST00000330688.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RARB	ENST00000330688.9	c.306+4198A>G		intron_variant		1	NM_000965.5	P1

Frequencies

GnomAD3 genomes AF: 0.876 AC: 133299 AN: 152144 Hom.: 58651 Cov.: 32

Gnomad AFR AF: 0.946

Gnomad AMI AF: 0.985

Gnomad AMR AF: 0.789

Gnomad ASJ AF: 0.858

Gnomad EAS AF: 0.866

Gnomad SAS AF: 0.807

Gnomad FIN AF: 0.870

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.859

Gnomad OTH AF: 0.881

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

GnomAD4 genome AF: 0.876 AC: 133402 AN: 152262 Hom.: 58700 Cov.: 32 AF XY: 0.875 AC XY: 65103 AN XY: 74430

Gnomad4 AFR AF: 0.946

Gnomad4 AMR AF: 0.788

Gnomad4 ASJ AF: 0.858

Gnomad4 EAS AF: 0.867

Gnomad4 SAS AF: 0.806

Gnomad4 FIN AF: 0.870

Gnomad4 NFE AF: 0.859

Gnomad4 OTH AF: 0.879

Alfa AF: 0.864 Hom.: 74177

Bravo AF: 0.872

Asia WGS AF: 0.810 AC: 2818 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.017
DANN	Benign	0.36

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: rs6778350; hg19: chr3-25507030;