rs13314219

Variant names:

• chr3-25454146-C-A
• rs13314219
• NM_000965.5:c.158-7047C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-25454146-C-A
• chr3-25454146-C-G
• chr3-25454146-C-T

Variant summary

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

The NM_000965.5(RARB):​c.158-7047C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 152,108 control chromosomes in the GnomAD database, including 31,520 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 0.64 (31520 hom., cov: 33)
• Consequence: RARB NM_000965.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06
• 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=-0.63).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RARB	NM_000965.5	c.158-7047C>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.158-7047C>A		intron_variant	Intron 1 of 7	1	NM_000965.5	ENSP00000332296.4

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97349 AN: 151988 Hom.: 31484 Cov.: 33

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.842

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.693

Gnomad EAS AF: 0.843

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.654

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

GnomAD4 genome AF: 0.641 AC: 97436 AN: 152108 Hom.: 31520 Cov.: 33 AF XY: 0.639 AC XY: 47500 AN XY: 74356

African (AFR) AF: 0.664 AC: 27517 AN: 41472

American (AMR) AF: 0.599 AC: 9154 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.693 AC: 2403 AN: 3470

East Asian (EAS) AF: 0.843 AC: 4376 AN: 5188

South Asian (SAS) AF: 0.619 AC: 2985 AN: 4822

European-Finnish (FIN) AF: 0.561 AC: 5928 AN: 10576

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.629 AC: 42722 AN: 67974

Other (OTH) AF: 0.654 AC: 1383 AN: 2114

Alfa AF: 0.632 Hom.: 128187

Bravo AF: 0.645

Asia WGS AF: 0.713 AC: 2480 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	9.9
DANN	Benign	0.72
PhyloP100		1.1
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: rs13314219; hg19: chr3-25495637;