rs6550978

Variant names:

• chr3-25449478-G-A
• rs6550978
• NM_000965.5:c.158-11715G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-25449478-G-A
• chr3-25449478-G-C

Variant summary

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

The NM_000965.5(RARB):​c.158-11715G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.682 in 151,778 control chromosomes in the GnomAD database, including 35,965 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 0.68 (35965 hom., cov: 31)
• Consequence: RARB NM_000965.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.615
• Publications: 4 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=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RARB	NM_000965.5	c.158-11715G>A		intron_variant	Intron 1 of 7	ENST00000330688.9	NP_000956.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RARB	ENST00000330688.9	c.158-11715G>A		intron_variant	Intron 1 of 7	1	NM_000965.5	ENSP00000332296.4

Frequencies

GnomAD3 genomes AF: 0.682 AC: 103383 AN: 151658 Hom.: 35937 Cov.: 31

Gnomad AFR AF: 0.812

Gnomad AMI AF: 0.838

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.827

Gnomad SAS AF: 0.659

Gnomad FIN AF: 0.645

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.693

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

GnomAD4 genome AF: 0.682 AC: 103469 AN: 151778 Hom.: 35965 Cov.: 31 AF XY: 0.683 AC XY: 50673 AN XY: 74144

African (AFR) AF: 0.812 AC: 33635 AN: 41414

American (AMR) AF: 0.612 AC: 9333 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 2225 AN: 3470

East Asian (EAS) AF: 0.828 AC: 4257 AN: 5140

South Asian (SAS) AF: 0.658 AC: 3161 AN: 4806

European-Finnish (FIN) AF: 0.645 AC: 6769 AN: 10496

Middle Eastern (MID) AF: 0.697 AC: 202 AN: 290

European-Non Finnish (NFE) AF: 0.614 AC: 41665 AN: 67900

Other (OTH) AF: 0.692 AC: 1461 AN: 2110

Alfa AF: 0.640 Hom.: 66708

Bravo AF: 0.686

Asia WGS AF: 0.721 AC: 2506 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	8.3
DANN	Benign	0.85
PhyloP100		0.61
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6550978; hg19: chr3-25490969;