rs10082776

Variant names:

• chr12-53227927-A-G
• rs10082776
• NM_000966.6:c.-142-240T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000966.6(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 NM_000966.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.341
• Publications: 10 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.542 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.-142-240T>C		intron	N/A	NP_000957.1	A8K3H3
	RARG	NM_001243730.2		c.-33+3242T>C		intron	N/A	NP_001230659.1	P13631-3
	RARG	NM_001243731.2		c.-31+3242T>C		intron	N/A	NP_001230660.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RARG	ENST00000425354.7	TSL:1 MANE Select	c.-142-240T>C		intron	N/A	ENSP00000388510.2	P13631-1
	RARG	ENST00000394426.5	TSL:1	c.-33+3242T>C		intron	N/A	ENSP00000377947.2	P13631-3
	RARG	ENST00000870211.1		c.-142-240T>C		intron	N/A	ENSP00000540270.1

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

African (AFR) AF: 0.548 AC: 22702 AN: 41456

American (AMR) AF: 0.201 AC: 3070 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0987 AC: 342 AN: 3464

East Asian (EAS) AF: 0.245 AC: 1266 AN: 5162

South Asian (SAS) AF: 0.343 AC: 1656 AN: 4832

European-Finnish (FIN) AF: 0.121 AC: 1277 AN: 10590

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.0859 AC: 5844 AN: 68002

Other (OTH) AF: 0.198 AC: 418 AN: 2108

Alfa AF: 0.139 Hom.: 9415

Bravo AF: 0.255

Asia WGS AF: 0.348 AC: 1207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.4
DANN	Benign	0.79
PhyloP100		-0.34
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: rs10082776; hg19: chr12-53621711;