rs1882119

chr12-52054024-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_173157.3(NR4A1):c.-2-303T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 384,162 control chromosomes in the GnomAD database, including 8,325 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 0.22 (5923 hom., cov: 33)
  • Exomes 𝑓: 0.12 (2402 hom.)
• Consequence: NR4A1 NM_173157.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.205

Genes affected

NR4A1 (HGNC:7980): (nuclear receptor subfamily 4 group A member 1) This gene encodes a member of the steroid-thyroid hormone-retinoid receptor superfamily. Expression is induced by phytohemagglutinin in human lymphocytes and by serum stimulation of arrested fibroblasts. The encoded protein acts as a nuclear transcription factor. Translocation of the protein from the nucleus to mitochondria induces apoptosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2011]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR4A1	NM_173157.3	c.-2-303T>C		intron_variant		ENST00000394825.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR4A1	ENST00000394825.6	c.-2-303T>C		intron_variant		1	NM_173157.3	P1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34110 AN: 152014 Hom.: 5913 Cov.: 33

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.185

GnomAD4 exome AF: 0.124 AC: 28843 AN: 232030 Hom.: 2402 Cov.: 0 AF XY: 0.124 AC XY: 14669 AN XY: 118294

Gnomad4 AFR exome AF: 0.470

Gnomad4 AMR exome AF: 0.0903

Gnomad4 ASJ exome AF: 0.143

Gnomad4 EAS exome AF: 0.125

Gnomad4 SAS exome AF: 0.160

Gnomad4 FIN exome AF: 0.115

Gnomad4 NFE exome AF: 0.105

Gnomad4 OTH exome AF: 0.133

GnomAD4 genome AF: 0.225 AC: 34155 AN: 152132 Hom.: 5923 Cov.: 33 AF XY: 0.222 AC XY: 16475 AN XY: 74362

Gnomad4 AFR AF: 0.492

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.189

Alfa AF: 0.194 Hom.: 728

Bravo AF: 0.231

Asia WGS AF: 0.184 AC: 643 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
Cadd	Benign	16
Dann	Benign	0.92

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: rs1882119; hg19: chr12-52447808;