rs6774513

Variant names:

• chr3-24844758-A-G
• rs6774513
• NM_001290216.3:c.-410-13916A>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.-410-13916A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,102 control chromosomes in the GnomAD database, including 2,723 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 0.17 (2723 hom., cov: 32)
• Consequence: RARB NM_001290216.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RARB	NM_001290216.3	c.-410-13916A>G		intron_variant	Intron 1 of 10		NP_001277145.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RARB	ENST00000383772.9	c.-458-13916A>G		intron_variant	Intron 1 of 11	5		ENSP00000373282.5
RARB	ENST00000686715.1	c.-531-13916A>G		intron_variant	Intron 1 of 11			ENSP00000510539.1
RARB	ENST00000687353.1	c.-531-13916A>G		intron_variant	Intron 2 of 12			ENSP00000508588.1

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25980 AN: 151984 Hom.: 2716 Cov.: 32

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.171 AC: 26026 AN: 152102 Hom.: 2723 Cov.: 32 AF XY: 0.173 AC XY: 12875 AN XY: 74344

African (AFR) AF: 0.273 AC: 11319 AN: 41462

American (AMR) AF: 0.180 AC: 2755 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 384 AN: 3472

East Asian (EAS) AF: 0.379 AC: 1957 AN: 5166

South Asian (SAS) AF: 0.146 AC: 702 AN: 4814

European-Finnish (FIN) AF: 0.116 AC: 1226 AN: 10592

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7142 AN: 68008

Other (OTH) AF: 0.166 AC: 351 AN: 2110

Alfa AF: 0.124 Hom.: 2386

Bravo AF: 0.180

Asia WGS AF: 0.222 AC: 774 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.5
DANN	Benign	0.38
PhyloP100		0.012

Splicing

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

Other links and lift over

dbSNP: rs6774513; hg19: chr3-24886249;