rs7340729

Variant names:

• chr3-24886049-G-C
• rs7340729
• NM_001290216.3:c.-332+27297G>C

Your query was ambiguous. Multiple possible variants found:

• chr3-24886049-G-C
• chr3-24886049-G-T

Variant summary

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

The NM_001290216.3(RARB):​c.-332+27297G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0763 in 152,150 control chromosomes in the GnomAD database, including 955 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 0.076 (955 hom., cov: 32)
• Consequence: RARB NM_001290216.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.295

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RARB	NM_001290216.3	c.-332+27297G>C		intron_variant	Intron 2 of 10		NP_001277145.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RARB	ENST00000383772.9	c.-380+27297G>C		intron_variant	Intron 2 of 11	5		ENSP00000373282.5
RARB	ENST00000686715.1	c.-453+27297G>C		intron_variant	Intron 2 of 11			ENSP00000510539.1
RARB	ENST00000687353.1	c.-453+27297G>C		intron_variant	Intron 3 of 12			ENSP00000508588.1

Frequencies

GnomAD3 genomes AF: 0.0761 AC: 11573 AN: 152032 Hom.: 952 Cov.: 32

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.0585

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.0338

Gnomad FIN AF: 0.00142

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0131

Gnomad OTH AF: 0.0874

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

GnomAD4 genome AF: 0.0763 AC: 11607 AN: 152150 Hom.: 955 Cov.: 32 AF XY: 0.0772 AC XY: 5738 AN XY: 74354

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.0585

Gnomad4 EAS AF: 0.326

Gnomad4 SAS AF: 0.0335

Gnomad4 FIN AF: 0.00142

Gnomad4 NFE AF: 0.0130

Gnomad4 OTH AF: 0.0879

Alfa AF: 0.00149 Hom.: 0

Bravo AF: 0.0917

Asia WGS AF: 0.155 AC: 537 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.5
DANN	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7340729; hg19: chr3-24927540;