rs748120

chr3-14993932-G-A

Variant summary

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

The NM_001291694.2(NR2C2):c.-39-9944G>A 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 152,008 control chromosomes in the GnomAD database, including 6,214 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 (6214 hom., cov: 31)
• Consequence: NR2C2 NM_001291694.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR2C2	NM_001291694.2	c.-39-9944G>A		intron_variant		ENST00000425241.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR2C2	ENST00000425241.6	c.-39-9944G>A		intron_variant		2	NM_001291694.2	P1

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40681 AN: 151890 Hom.: 6188 Cov.: 31

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.295

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

GnomAD4 genome AF: 0.268 AC: 40753 AN: 152008 Hom.: 6214 Cov.: 31 AF XY: 0.260 AC XY: 19310 AN XY: 74286

Gnomad4 AFR AF: 0.401

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.284

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.237

Gnomad4 OTH AF: 0.297

Alfa AF: 0.238 Hom.: 2131

Bravo AF: 0.285

Asia WGS AF: 0.180 AC: 626 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.021
Dann	Benign	0.33

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: rs748120; hg19: chr3-15035439;