3-25143957-T-C

Variant names:

• chr3-25143957-T-C
• rs9310772
• NM_001290216.3:c.-279-30162T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001290216.3(RARB):​c.-279-30162T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 152,054 control chromosomes in the GnomAD database, including 48,238 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 0.80 (48238 hom., cov: 32)
• Consequence: RARB NM_001290216.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.242
• Publications: 2 publications found

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]

RARB Gene-Disease associations (from GenCC):

• microphthalmia, syndromic 12

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen, Baylor College of Medicine Research Center
• Matthew-Wood syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RARB	NM_001290216.3	c.-279-30162T>C		intron_variant	Intron 3 of 10		NP_001277145.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RARB	ENST00000383772.9	c.-280+11749T>C		intron_variant	Intron 4 of 11	5		ENSP00000373282.5
RARB	ENST00000686715.1	c.-279-30162T>C		intron_variant	Intron 4 of 11			ENSP00000510539.1
RARB	ENST00000687353.1	c.-279-30162T>C		intron_variant	Intron 5 of 12			ENSP00000508588.1

Frequencies

GnomAD3 genomes AF: 0.795 AC: 120851 AN: 151940 Hom.: 48205 Cov.: 32

Gnomad AFR AF: 0.722

Gnomad AMI AF: 0.863

Gnomad AMR AF: 0.836

Gnomad ASJ AF: 0.884

Gnomad EAS AF: 0.824

Gnomad SAS AF: 0.749

Gnomad FIN AF: 0.791

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.827

Gnomad OTH AF: 0.810

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

GnomAD4 genome AF: 0.795 AC: 120936 AN: 152054 Hom.: 48238 Cov.: 32 AF XY: 0.792 AC XY: 58894 AN XY: 74320

African (AFR) AF: 0.722 AC: 29910 AN: 41442

American (AMR) AF: 0.836 AC: 12783 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.884 AC: 3069 AN: 3472

East Asian (EAS) AF: 0.823 AC: 4252 AN: 5164

South Asian (SAS) AF: 0.751 AC: 3609 AN: 4808

European-Finnish (FIN) AF: 0.791 AC: 8364 AN: 10574

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.827 AC: 56224 AN: 67986

Other (OTH) AF: 0.812 AC: 1715 AN: 2112

Alfa AF: 0.815 Hom.: 154859

Bravo AF: 0.796

Asia WGS AF: 0.792 AC: 2754 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.77
DANN	Benign	0.42
PhyloP100		-0.24

Splicing

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

Other links and lift over

dbSNP: rs9310772; hg19: chr3-25185448;