rs1283155

Positions:

• chr12-52045965-G-A
• chr12-52045965-G-T

Variant summary

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

The ENST00000478250.1(NR4A1):​n.185+2054G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,136 control chromosomes in the GnomAD database, including 6,141 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 (6141 hom., cov: 33)
• Consequence: NR4A1 ENST00000478250.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.10

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR4A1	XM_017019248.2	c.*243G>A		3_prime_UTR_variant	4/4
NR4A1	XM_017019249.2	c.*243G>A		3_prime_UTR_variant	4/4
NR4A1	NM_001202233.2	c.37+4036G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR4A1	ENST00000478250.1	n.185+2054G>A		intron_variant, non_coding_transcript_variant		1
NR4A1	ENST00000549102.1	n.487+2054G>A		intron_variant, non_coding_transcript_variant		1
NR4A1	ENST00000360284.7	c.37+4036G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41247 AN: 152020 Hom.: 6126 Cov.: 33

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.277

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.271 AC: 41300 AN: 152136 Hom.: 6141 Cov.: 33 AF XY: 0.279 AC XY: 20749 AN XY: 74362

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.465

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.393

Gnomad4 SAS AF: 0.352

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.287

Alfa AF: 0.254 Hom.: 7422

Bravo AF: 0.290

Asia WGS AF: 0.348 AC: 1211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.44
DANN	Benign	0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1283155; hg19: chr12-52439749;