rs1465057

Variant names:

• chr12-53219097-T-C
• rs1465057
• NM_000966.6:c.185-3303A>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.185-3303A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 152,020 control chromosomes in the GnomAD database, including 6,913 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 0.23 (6913 hom., cov: 32)
• Consequence: RARG NM_000966.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365
• Publications: 12 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=-0.62).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RARG	NM_000966.6	c.185-3303A>G		intron_variant	Intron 3 of 9	ENST00000425354.7	NP_000957.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RARG	ENST00000425354.7	c.185-3303A>G		intron_variant	Intron 3 of 9	1	NM_000966.6	ENSP00000388510.2

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35295 AN: 151902 Hom.: 6876 Cov.: 32

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.0737

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.0940

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.233 AC: 35386 AN: 152020 Hom.: 6913 Cov.: 32 AF XY: 0.233 AC XY: 17285 AN XY: 74320

African (AFR) AF: 0.534 AC: 22132 AN: 41410

American (AMR) AF: 0.209 AC: 3191 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 348 AN: 3470

East Asian (EAS) AF: 0.164 AC: 848 AN: 5162

South Asian (SAS) AF: 0.235 AC: 1133 AN: 4822

European-Finnish (FIN) AF: 0.0737 AC: 780 AN: 10590

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.0940 AC: 6389 AN: 67956

Other (OTH) AF: 0.196 AC: 414 AN: 2110

Alfa AF: 0.131 Hom.: 3553

Bravo AF: 0.253

Asia WGS AF: 0.262 AC: 910 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	12
DANN	Benign	0.80
PhyloP100		0.36
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		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: rs1465057; hg19: chr12-53612881;