rs1153594

Variant names:

• chr3-25518437-C-T
• rs1153594
• NM_000965.5:c.448+17114C>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.448+17114C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 151,884 control chromosomes in the GnomAD database, including 3,477 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 0.19 (3477 hom., cov: 32)
• Consequence: RARB NM_000965.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.499
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RARB	NM_000965.5	c.448+17114C>T		intron_variant	Intron 3 of 7	ENST00000330688.9	NP_000956.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RARB	ENST00000330688.9	c.448+17114C>T		intron_variant	Intron 3 of 7	1	NM_000965.5	ENSP00000332296.4

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29351 AN: 151766 Hom.: 3467 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.0780

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.0931

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.194 AC: 29393 AN: 151884 Hom.: 3477 Cov.: 32 AF XY: 0.195 AC XY: 14496 AN XY: 74208

African (AFR) AF: 0.301 AC: 12437 AN: 41382

American (AMR) AF: 0.278 AC: 4239 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.0931 AC: 323 AN: 3468

East Asian (EAS) AF: 0.336 AC: 1735 AN: 5160

South Asian (SAS) AF: 0.110 AC: 531 AN: 4814

European-Finnish (FIN) AF: 0.138 AC: 1457 AN: 10548

Middle Eastern (MID) AF: 0.154 AC: 45 AN: 292

European-Non Finnish (NFE) AF: 0.120 AC: 8169 AN: 67948

Other (OTH) AF: 0.183 AC: 386 AN: 2108

Alfa AF: 0.150 Hom.: 2621

Bravo AF: 0.213

Asia WGS AF: 0.238 AC: 823 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.4
DANN	Benign	0.80
PhyloP100		-0.50
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: rs1153594; hg19: chr3-25559928;