rs3741434

Variant names:

• chr12-53211560-T-C
• rs3741434
• NM_000966.6:c.*116A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000966.6. 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
	RARG	NM_000966.6	MANE Select	c.*116A>G		3_prime_UTR	Exon 10 of 10	NP_000957.1	A8K3H3
	RARG	NM_001042728.3		c.*116A>G		3_prime_UTR	Exon 8 of 8	NP_001036193.1	P13631-2
	RARG	NM_001243732.2		c.*116A>G		3_prime_UTR	Exon 7 of 7	NP_001230661.1	P13631-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RARG	ENST00000425354.7	TSL:1 MANE Select	c.*116A>G		3_prime_UTR	Exon 10 of 10	ENSP00000388510.2	P13631-1
	RARG	ENST00000338561.9	TSL:1	c.*116A>G		3_prime_UTR	Exon 8 of 8	ENSP00000343698.5	P13631-2
	RARG	ENST00000394426.5	TSL:1	c.*116A>G		3_prime_UTR	Exon 9 of 9	ENSP00000377947.2	P13631-3

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

African (AFR) AF: 0.162 AC: 2845 AN: 17540

American (AMR) AF: 0.151 AC: 1467 AN: 9728

Ashkenazi Jewish (ASJ) AF: 0.0999 AC: 1438 AN: 14396

East Asian (EAS) AF: 0.0922 AC: 2368 AN: 25686

South Asian (SAS) AF: 0.0655 AC: 2336 AN: 35678

European-Finnish (FIN) AF: 0.115 AC: 3230 AN: 28194

Middle Eastern (MID) AF: 0.111 AC: 295 AN: 2664

European-Non Finnish (NFE) AF: 0.141 AC: 96666 AN: 687426

Other (OTH) AF: 0.131 AC: 4938 AN: 37626

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

African (AFR) AF: 0.162 AC: 6720 AN: 41426

American (AMR) AF: 0.128 AC: 1961 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0987 AC: 342 AN: 3466

East Asian (EAS) AF: 0.0679 AC: 350 AN: 5154

South Asian (SAS) AF: 0.0654 AC: 315 AN: 4814

European-Finnish (FIN) AF: 0.102 AC: 1083 AN: 10586

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9586 AN: 67894

Other (OTH) AF: 0.137 AC: 290 AN: 2114

Alfa AF: 0.138 Hom.: 2794

Bravo AF: 0.144

Asia WGS AF: 0.0700 AC: 244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	14
DANN	Benign	0.83
PhyloP100		0.080
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: rs3741434; hg19: chr12-53605344; COSMIC: COSV57238940; COSMIC: COSV57238940;