rs6797081

Variant names:

• chr3-24957232-A-G
• rs6797081
• NM_001290216.3:c.-332+98480A>G

Variant summary

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

The NM_001290216.3(RARB):​c.-332+98480A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 152,018 control chromosomes in the GnomAD database, including 16,412 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 0.46 (16412 hom., cov: 32)
• Consequence: RARB NM_001290216.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0430
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RARB	NM_001290216.3	c.-332+98480A>G		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+98480A>G		intron_variant	Intron 2 of 11	5		ENSP00000373282.5
RARB	ENST00000686715.1	c.-453+98480A>G		intron_variant	Intron 2 of 11			ENSP00000510539.1
RARB	ENST00000687353.1	c.-453+98480A>G		intron_variant	Intron 3 of 12			ENSP00000508588.1

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69327 AN: 151900 Hom.: 16384 Cov.: 32

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.607

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.417

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

GnomAD4 genome AF: 0.457 AC: 69415 AN: 152018 Hom.: 16412 Cov.: 32 AF XY: 0.456 AC XY: 33881 AN XY: 74324

African (AFR) AF: 0.514 AC: 21310 AN: 41422

American (AMR) AF: 0.316 AC: 4823 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 985 AN: 3468

East Asian (EAS) AF: 0.608 AC: 3151 AN: 5180

South Asian (SAS) AF: 0.510 AC: 2454 AN: 4816

European-Finnish (FIN) AF: 0.486 AC: 5136 AN: 10564

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.443 AC: 30099 AN: 67968

Other (OTH) AF: 0.423 AC: 893 AN: 2112

Alfa AF: 0.429 Hom.: 3593

Bravo AF: 0.447

Asia WGS AF: 0.553 AC: 1921 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.51
PhyloP100		0.043

Splicing

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

Other links and lift over

dbSNP: rs6797081; hg19: chr3-24998723;