rs3741434

Positions:

• chr12-53211560-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000966.6(RARG):​c.*116A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 1,010,878 control chromosomes in the GnomAD database, including 9,696 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 0.14 (1457 hom., cov: 32)
  • Exomes 𝑓: 0.13 (8239 hom.)
• Consequence: RARG NM_000966.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0800

Genes affected

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]

RARG (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RARG	NM_000966.6	c.*116A>G		3_prime_UTR_variant	10/10	ENST00000425354.7	NP_000957.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RARG	ENST00000425354	c.*116A>G		3_prime_UTR_variant	10/10	1	NM_000966.6	ENSP00000388510.2

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20734 AN: 151820 Hom.: 1452 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.0969

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.0987

Gnomad EAS AF: 0.0681

Gnomad SAS AF: 0.0654

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.136

GnomAD4 exome AF: 0.135 AC: 115583 AN: 858938 Hom.: 8239 Cov.: 11 AF XY: 0.133 AC XY: 55743 AN XY: 420232

Gnomad4 AFR exome AF: 0.162

Gnomad4 AMR exome AF: 0.151

Gnomad4 ASJ exome AF: 0.0999

Gnomad4 EAS exome AF: 0.0922

Gnomad4 SAS exome AF: 0.0655

Gnomad4 FIN exome AF: 0.115

Gnomad4 NFE exome AF: 0.141

Gnomad4 OTH exome AF: 0.131

GnomAD4 genome AF: 0.137 AC: 20762 AN: 151940 Hom.: 1457 Cov.: 32 AF XY: 0.133 AC XY: 9843 AN XY: 74282

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.0987

Gnomad4 EAS AF: 0.0679

Gnomad4 SAS AF: 0.0654

Gnomad4 FIN AF: 0.102

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.137

Alfa AF: 0.138 Hom.: 1974

Bravo AF: 0.144

Asia WGS AF: 0.0700 AC: 244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	14
DANN	Benign	0.83

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

Publications

LitVar

Other links and lift over

dbSNP: rs3741434; hg19: chr12-53605344; COSMIC: COSV57238940; COSMIC: COSV57238940;