rs1868852806

Variant names:

• chr12-95022326-C-A
• rs1868852806
• NM_003297.4:c.1715G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-95022326-C-A
• chr12-95022326-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_003297.4(NR2C1):​c.1715G>T​(p.Gly572Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G572S) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: NR2C1 NM_003297.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91
• Publications: 0 publications found

Genes affected

NR2C1 (HGNC:7971): (nuclear receptor subfamily 2 group C member 1) This gene encodes a nuclear hormone receptor characterized by a highly conserved DNA binding domain (DBD), a variable hinge region, and a carboxy-terminal ligand binding domain (LBD) that is typical for all members of the steroid/thyroid hormone receptor superfamily. This protein also belongs to a large family of ligand-inducible transcription factors that regulate gene expression by binding to specific DNA sequences within promoters of target genes. Multiple alternatively spliced transcript variants have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.848

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003297.4. 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
	NR2C1	NM_003297.4	MANE Select	c.1715G>T	p.Gly572Val	missense	Exon 14 of 14	NP_003288.2	P13056-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR2C1	ENST00000333003.10	TSL:2 MANE Select	c.1715G>T	p.Gly572Val	missense	Exon 14 of 14	ENSP00000333275.4	P13056-1
	NR2C1	ENST00000922903.1		c.1847G>T	p.Gly616Val	missense	Exon 15 of 15	ENSP00000592962.1
	NR2C1	ENST00000922904.1		c.1847G>T	p.Gly616Val	missense	Exon 15 of 15	ENSP00000592963.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152034 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152034 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74242

African (AFR) AF: 0.0000242 AC: 1 AN: 41384

American (AMR) AF: 0.00 AC: 0 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10558

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.87	D
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.060	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Benign	-0.33	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		7.9
PrimateAI	Pathogenic	0.87	D
PROVEAN	Pathogenic	-6.3	D
REVEL	Pathogenic	0.67
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.012	D
Polyphen		1.0	D
Vest4		0.88
MutPred		0.56		Gain of catalytic residue at N576 (P = 0)
MVP		0.67
MPC		0.83
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.91
gMVP		0.86
Mutation Taster		=33/67	disease causing

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: rs1868852806; hg19: chr12-95416102; COSMIC: COSV100280553; COSMIC: COSV100280553;