rs10082776

Positions:

• chr12-53227927-A-G

Variant summary

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

The ENST00000425354.7(RARG):​c.-142-240T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 152,106 control chromosomes in the GnomAD database, including 7,491 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 0.24 (7491 hom., cov: 32)
• Consequence: RARG ENST00000425354.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.341

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RARG	NM_000966.6	c.-142-240T>C		intron_variant		ENST00000425354.7	NP_000957.1
RARG	NM_001243730.2	c.-33+3242T>C		intron_variant			NP_001230659.1
RARG	NM_001243731.2	c.-31+3242T>C		intron_variant			NP_001230660.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RARG	ENST00000425354.7	c.-142-240T>C		intron_variant		1	NM_000966.6	ENSP00000388510	A2

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36637 AN: 151986 Hom.: 7440 Cov.: 32

Gnomad AFR AF: 0.547

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.0987

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.0859

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.242 AC: 36760 AN: 152106 Hom.: 7491 Cov.: 32 AF XY: 0.245 AC XY: 18197 AN XY: 74350

Gnomad4 AFR AF: 0.548

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.0987

Gnomad4 EAS AF: 0.245

Gnomad4 SAS AF: 0.343

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.0859

Gnomad4 OTH AF: 0.198

Alfa AF: 0.117 Hom.: 2556

Bravo AF: 0.255

Asia WGS AF: 0.348 AC: 1207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.4
DANN	Benign	0.79

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: rs10082776; hg19: chr12-53621711;