rs6580936

Variant names:

• chr12-53224045-A-G
• rs6580936
• NM_000966.6:c.184+3317T>C

Your query was ambiguous. Multiple possible variants found:

• chr12-53224045-A-G
• chr12-53224045-A-T

Variant summary

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

The NM_000966.6(RARG):​c.184+3317T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 152,018 control chromosomes in the GnomAD database, including 12,511 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 0.34 (12511 hom., cov: 31)
• Consequence: RARG NM_000966.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.162
• Publications: 13 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.66 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.184+3317T>C		intron	N/A	NP_000957.1	A8K3H3
	RARG	NM_001243730.2		c.-33+7124T>C		intron	N/A	NP_001230659.1	P13631-3
	RARG	NM_001243731.2		c.-31+7124T>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.184+3317T>C		intron	N/A	ENSP00000388510.2	P13631-1
	RARG	ENST00000394426.5	TSL:1	c.-33+7124T>C		intron	N/A	ENSP00000377947.2	P13631-3
	RARG	ENST00000870211.1		c.184+3317T>C		intron	N/A	ENSP00000540270.1

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52230 AN: 151898 Hom.: 12468 Cov.: 31

Gnomad AFR AF: 0.666

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.275

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

GnomAD4 genome AF: 0.344 AC: 52340 AN: 152018 Hom.: 12511 Cov.: 31 AF XY: 0.354 AC XY: 26298 AN XY: 74300

African (AFR) AF: 0.667 AC: 27623 AN: 41426

American (AMR) AF: 0.317 AC: 4854 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 678 AN: 3472

East Asian (EAS) AF: 0.362 AC: 1870 AN: 5162

South Asian (SAS) AF: 0.472 AC: 2274 AN: 4820

European-Finnish (FIN) AF: 0.280 AC: 2960 AN: 10578

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11164 AN: 67962

Other (OTH) AF: 0.278 AC: 585 AN: 2104

Alfa AF: 0.219 Hom.: 8770

Bravo AF: 0.354

Asia WGS AF: 0.471 AC: 1636 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.50
PhyloP100		-0.16
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: rs6580936; hg19: chr12-53617829; COSMIC: COSV58435211; COSMIC: COSV58435211;