rs1978782

Variant names:

• chr3-14956899-G-C
• rs1978782
• NM_001291694.2:c.-40+8993G>C

Variant summary

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

The ENST00000425241.6(NR2C2):​c.-40+8993G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 152,128 control chromosomes in the GnomAD database, including 6,228 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 0.27 (6228 hom., cov: 33)
• Consequence: NR2C2 ENST00000425241.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.412
• Publications: 2 publications found

Genes affected

NR2C2 (HGNC:7972): (nuclear receptor subfamily 2 group C member 2) This gene encodes a protein that belongs to the nuclear hormone receptor family. Members of this family act as ligand-activated transcription factors and function in many biological processes such as development, cellular differentiation and homeostasis. The activated receptor/ligand complex is translocated to the nucleus where it binds to hormone response elements of target genes. The protein encoded by this gene plays a role in protecting cells from oxidative stress and damage induced by ionizing radiation. The lack of a similar gene in mouse results in growth retardation, severe spinal curvature, subfertility, premature aging, and prostatic intraepithelial neoplasia (PIN) development. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000425241.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR2C2	NM_001291694.2	MANE Select	c.-40+8993G>C		intron	N/A	NP_001278623.1
	NR2C2	NM_003298.5		c.-40+8993G>C		intron	N/A	NP_003289.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR2C2	ENST00000425241.6	TSL:2 MANE Select	c.-40+8993G>C		intron	N/A	ENSP00000388387.1
	NR2C2	ENST00000323373.10	TSL:1	c.-40+8993G>C		intron	N/A	ENSP00000320447.6
	NR2C2	ENST00000413118.5	TSL:4	c.-40+8993G>C		intron	N/A	ENSP00000402272.1

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40625 AN: 152010 Hom.: 6195 Cov.: 33

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.0965

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.268 AC: 40705 AN: 152128 Hom.: 6228 Cov.: 33 AF XY: 0.260 AC XY: 19308 AN XY: 74378

African (AFR) AF: 0.405 AC: 16808 AN: 41470

American (AMR) AF: 0.232 AC: 3550 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 920 AN: 3468

East Asian (EAS) AF: 0.136 AC: 703 AN: 5178

South Asian (SAS) AF: 0.141 AC: 680 AN: 4828

European-Finnish (FIN) AF: 0.0965 AC: 1021 AN: 10584

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.235 AC: 15982 AN: 68006

Other (OTH) AF: 0.293 AC: 618 AN: 2110

Alfa AF: 0.243 Hom.: 634

Bravo AF: 0.286

Asia WGS AF: 0.181 AC: 631 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.56
PhyloP100		-0.41
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: rs1978782; hg19: chr3-14998406;