12-53233156-C-T

Variant names:

• chr12-53233156-C-T
• rs11170488
• ENST00000768428.1:n.98+674C>T

Variant summary

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

The ENST00000768428.1(ENSG00000300047):​n.98+674C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 151,788 control chromosomes in the GnomAD database, including 5,725 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 0.27 (5725 hom., cov: 31)
• Consequence: ENSG00000300047 ENST00000768428.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.48
• Publications: 4 publications found

Genes affected

ENSG00000300047 (HGNC:):

RARG (HGNC:9866): (retinoic acid receptor gamma) This gene encodes a retinoic acid receptor that belongs to the nuclear hormone receptor family. Retinoic acid receptors (RARs) act as ligand-dependent transcriptional regulators. When bound to ligands, RARs activate transcription by binding as heterodimers to the retinoic acid response elements (RARE) found in the promoter regions of the target genes. In their unbound form, RARs repress transcription of their target genes. RARs are involved in various biological processes, including limb bud development, skeletal growth, and matrix homeostasis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000768428.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000300047	ENST00000768428.1		n.98+674C>T		intron	N/A
	RARG	ENST00000959620.1		c.-818G>A		upstream_gene	N/A	ENSP00000629679.1
	RARG	ENST00000959621.1		c.-964G>A		upstream_gene	N/A	ENSP00000629680.1

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40518 AN: 151670 Hom.: 5706 Cov.: 31

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.267 AC: 40564 AN: 151788 Hom.: 5725 Cov.: 31 AF XY: 0.271 AC XY: 20132 AN XY: 74190

African (AFR) AF: 0.248 AC: 10241 AN: 41362

American (AMR) AF: 0.242 AC: 3693 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 876 AN: 3462

East Asian (EAS) AF: 0.538 AC: 2776 AN: 5156

South Asian (SAS) AF: 0.439 AC: 2114 AN: 4812

European-Finnish (FIN) AF: 0.282 AC: 2963 AN: 10510

Middle Eastern (MID) AF: 0.308 AC: 90 AN: 292

European-Non Finnish (NFE) AF: 0.251 AC: 17014 AN: 67916

Other (OTH) AF: 0.270 AC: 569 AN: 2106

Alfa AF: 0.257 Hom.: 7502

Bravo AF: 0.263

Asia WGS AF: 0.480 AC: 1668 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.64
DANN	Benign	0.62
PhyloP100		-2.5
PromoterAI		-0.16	Neutral

Splicing

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

Other links and lift over

dbSNP: rs11170488; hg19: chr12-53626940;