rs1465057

chr12-53219097-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.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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
RARG	NM_000966.6	c.185-3303A>G		intron_variant		ENST00000425354.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RARG	ENST00000425354.7	c.185-3303A>G		intron_variant		1	NM_000966.6	A2

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

Gnomad4 AFR AF: 0.534

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.100

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.235

Gnomad4 FIN AF: 0.0737

Gnomad4 NFE AF: 0.0940

Gnomad4 OTH AF: 0.196

Alfa AF: 0.118 Hom.: 2162

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1465057; hg19: chr12-53612881;