ENST00000549102.1:n.283G>A

Variant names:

• chr12-52043707-G-A
• rs2242107
• ENST00000549102.1:n.283G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000549102.1(NR4A1):​n.283G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 1,261,206 control chromosomes in the GnomAD database, including 71,339 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 0.41 (14782 hom., cov: 33)
  • Exomes 𝑓: 0.31 (56557 hom.)
• Consequence: NR4A1 ENST00000549102.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.30
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000549102.1. 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
	NR4A1	NM_001202234.2		c.160+1778G>A		intron	N/A	NP_001189163.1
	NR4A1	NM_001202233.2		c.37+1778G>A		intron	N/A	NP_001189162.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR4A1	ENST00000549102.1	TSL:1	n.283G>A		non_coding_transcript_exon	Exon 1 of 2
	NR4A1	ENST00000545748.5	TSL:2	c.160+1778G>A		intron	N/A	ENSP00000440864.1
	NR4A1	ENST00000360284.7	TSL:2	c.37+1778G>A		intron	N/A	ENSP00000353427.3

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62905 AN: 151964 Hom.: 14739 Cov.: 33

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.322

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.397

GnomAD4 exome AF: 0.308 AC: 341473 AN: 1109122 Hom.: 56557 Cov.: 32 AF XY: 0.310 AC XY: 168196 AN XY: 542500

African (AFR) AF: 0.626 AC: 14548 AN: 23228

American (AMR) AF: 0.602 AC: 14522 AN: 24120

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 4785 AN: 13796

East Asian (EAS) AF: 0.481 AC: 6122 AN: 12716

South Asian (SAS) AF: 0.423 AC: 30453 AN: 72010

European-Finnish (FIN) AF: 0.279 AC: 3213 AN: 11522

Middle Eastern (MID) AF: 0.343 AC: 892 AN: 2604

European-Non Finnish (NFE) AF: 0.279 AC: 253683 AN: 908992

Other (OTH) AF: 0.330 AC: 13255 AN: 40134

GnomAD4 genome AF: 0.414 AC: 63016 AN: 152084 Hom.: 14782 Cov.: 33 AF XY: 0.419 AC XY: 31175 AN XY: 74342

African (AFR) AF: 0.617 AC: 25587 AN: 41484

American (AMR) AF: 0.519 AC: 7928 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 1236 AN: 3468

East Asian (EAS) AF: 0.485 AC: 2506 AN: 5164

South Asian (SAS) AF: 0.406 AC: 1956 AN: 4814

European-Finnish (FIN) AF: 0.288 AC: 3048 AN: 10584

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.286 AC: 19408 AN: 67970

Other (OTH) AF: 0.399 AC: 841 AN: 2110

Alfa AF: 0.322 Hom.: 13036

Bravo AF: 0.442

Asia WGS AF: 0.467 AC: 1623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	20
DANN	Benign	0.82
PhyloP100		3.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2242107; hg19: chr12-52437491;