rs744690

Variant names:

• chr12-52047700-T-G
• rs744690
• ENST00000478250.1:n.185+3789T>G

Variant summary

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

The ENST00000478250.1(NR4A1):​n.185+3789T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,166 control chromosomes in the GnomAD database, including 3,348 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 0.18 (3348 hom., cov: 33)
• Consequence: NR4A1 ENST00000478250.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.355
• Publications: 5 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]

ENSG00000306678 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000478250.1. 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+5771T>G		intron	N/A	NP_001189163.1
	NR4A1	NM_001202233.2		c.37+5771T>G		intron	N/A	NP_001189162.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR4A1	ENST00000478250.1	TSL:1	n.185+3789T>G		intron	N/A
	NR4A1	ENST00000549102.1	TSL:1	n.487+3789T>G		intron	N/A
	NR4A1	ENST00000545748.5	TSL:2	c.160+5771T>G		intron	N/A	ENSP00000440864.1

Frequencies

GnomAD3 genomes AF: 0.184 AC: 28000 AN: 152048 Hom.: 3330 Cov.: 33

Gnomad AFR AF: 0.0956

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.201

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

GnomAD4 genome AF: 0.184 AC: 28030 AN: 152166 Hom.: 3348 Cov.: 33 AF XY: 0.193 AC XY: 14341 AN XY: 74402

African (AFR) AF: 0.0955 AC: 3965 AN: 41534

American (AMR) AF: 0.389 AC: 5951 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 705 AN: 3470

East Asian (EAS) AF: 0.417 AC: 2151 AN: 5162

South Asian (SAS) AF: 0.269 AC: 1297 AN: 4818

European-Finnish (FIN) AF: 0.188 AC: 1997 AN: 10596

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.165 AC: 11244 AN: 67976

Other (OTH) AF: 0.198 AC: 420 AN: 2116

Alfa AF: 0.171 Hom.: 1222

Bravo AF: 0.202

Asia WGS AF: 0.317 AC: 1103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	13
DANN	Benign	0.87
PhyloP100		0.35
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: rs744690; hg19: chr12-52441484;