rs7613553

Variant names:

• chr3-25435921-C-A
• rs7613553
• NM_000965.5:c.157+7033C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-25435921-C-A
• chr3-25435921-C-G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_000965.5(RARB):​c.157+7033C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 151,952 control chromosomes in the GnomAD database, including 11,169 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 0.37 (11169 hom., cov: 32)
• Consequence: RARB NM_000965.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06
• Publications: 5 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RARB	NM_000965.5	c.157+7033C>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.157+7033C>A		intron_variant	Intron 1 of 7	1	NM_000965.5	ENSP00000332296.4

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56222 AN: 151834 Hom.: 11153 Cov.: 32

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.383

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

GnomAD4 genome AF: 0.370 AC: 56265 AN: 151952 Hom.: 11169 Cov.: 32 AF XY: 0.369 AC XY: 27407 AN XY: 74230

African (AFR) AF: 0.271 AC: 11239 AN: 41436

American (AMR) AF: 0.314 AC: 4790 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 1472 AN: 3466

East Asian (EAS) AF: 0.133 AC: 689 AN: 5184

South Asian (SAS) AF: 0.378 AC: 1822 AN: 4818

European-Finnish (FIN) AF: 0.464 AC: 4882 AN: 10516

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.446 AC: 30285 AN: 67942

Other (OTH) AF: 0.381 AC: 804 AN: 2112

Alfa AF: 0.409 Hom.: 39438

Bravo AF: 0.350

Asia WGS AF: 0.272 AC: 946 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	15
DANN	Benign	0.64
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: rs7613553; hg19: chr3-25477412;