rs748120

Variant names:

• chr3-14993932-G-A
• rs748120
• NM_001291694.2:c.-39-9944G>A

Variant summary

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

The NM_003298.5(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_003298.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 8 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003298.5. 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.-39-9944G>A		intron	N/A	NP_001278623.1
	NR2C2	NM_003298.5		c.-39-9944G>A		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.-39-9944G>A		intron	N/A	ENSP00000388387.1
	NR2C2	ENST00000323373.10	TSL:1	c.-39-9944G>A		intron	N/A	ENSP00000320447.6
	NR2C2	ENST00000859246.1		c.-39-9944G>A		intron	N/A	ENSP00000529305.1

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

African (AFR) AF: 0.401 AC: 16615 AN: 41442

American (AMR) AF: 0.234 AC: 3571 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 985 AN: 3470

East Asian (EAS) AF: 0.111 AC: 573 AN: 5158

South Asian (SAS) AF: 0.148 AC: 715 AN: 4824

European-Finnish (FIN) AF: 0.109 AC: 1152 AN: 10570

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16087 AN: 67964

Other (OTH) AF: 0.297 AC: 625 AN: 2104

Alfa AF: 0.241 Hom.: 2445

Bravo AF: 0.285

Asia WGS AF: 0.180 AC: 626 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	0.021
DANN	Benign	0.33
PhyloP100		-1.3
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: rs748120; hg19: chr3-15035439;