rs2603751

chr12-52059498-T-C

Variant summary

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

The NM_173157.3(NR4A1):c.*554T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 152,116 control chromosomes in the GnomAD database, including 7,060 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 0.24 (7059 hom., cov: 33)
  • Exomes 𝑓: 0.071 (1 hom.)
• Consequence: NR4A1 NM_173157.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.273

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]

NR4A1AS (HGNC:54409): (NR4A1 antisense RNA)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR4A1	NM_173157.3	c.*554T>C		3_prime_UTR_variant	7/7	ENST00000394825.6
NR4A1AS	NR_170321.1	n.3A>G		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR4A1	ENST00000394825.6	c.*554T>C		3_prime_UTR_variant	7/7	1	NM_173157.3	P1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36443 AN: 151956 Hom.: 7042 Cov.: 33

Gnomad AFR AF: 0.543

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.195

GnomAD4 exome AF: 0.0714 AC: 3 AN: 42 Hom.: 1 Cov.: 0 AF XY: 0.111 AC XY: 2 AN XY: 18

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0789

GnomAD4 genome AF: 0.240 AC: 36504 AN: 152074 Hom.: 7059 Cov.: 33 AF XY: 0.237 AC XY: 17617 AN XY: 74336

Gnomad4 AFR AF: 0.543

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.103

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.200

Alfa AF: 0.137 Hom.: 2367

Bravo AF: 0.250

Asia WGS AF: 0.189 AC: 659 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
Cadd	Benign	15
Dann	Benign	0.82

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: rs2603751; hg19: chr12-52453282;