Genetic Variant ENST00000550557.1:n.607T>C (chr12-52054024-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000550557.1(NR4A1):n.607T>C 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 0.164 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
ENST00000550557.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.205

Publications

5 publications found

Variant links:

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]

NR4A1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NR4A1	NM_173157.3 link	c.-2-303T>C		intron_variant	Intron 1 of 6	ENST00000394825.6	NP_775180.1	P22736-1A0A024R126

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR4A1	ENST00000394825.6 link	c.-2-303T>C		intron_variant	Intron 1 of 6	1	NM_173157.3	ENSP00000378302.1		P22736-1

Frequencies

GnomAD3 genomes

AF:

0.224

AC:

34110

AN:

152014

Hom.:

5913

Cov.:

show subpopulations

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.:

AF XY:

0.124

AC XY:

14669

AN XY:

118294

show subpopulations

African (AFR)

AF:

0.470

AC:

3237

AN:

6880

American (AMR)

AF:

0.0903

AC:

738

AN:

8174

Ashkenazi Jewish (ASJ)

AF:

0.143

AC:

1163

AN:

8128

East Asian (EAS)

AF:

0.125

AC:

2218

AN:

17748

South Asian (SAS)

AF:

0.160

AC:

2209

AN:

13810

European-Finnish (FIN)

AF:

0.115

AC:

1834

AN:

15882

Middle Eastern (MID)

AF:

0.157

AC:

182

AN:

1158

European-Non Finnish (NFE)

AF:

0.105

AC:

15318

AN:

145590

Other (OTH)

AF:

0.133

AC:

1944

AN:

14660

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

1149

2298

3448

4597

5746

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

140

280

420

560

700

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.225

AC:

34155

AN:

152132

Hom.:

5923

Cov.:

AF XY:

0.222

AC XY:

16475

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.492

AC:

20406

AN:

41484

American (AMR)

AF:

0.125

AC:

1908

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.158

AC:

550

AN:

3472

East Asian (EAS)

AF:

0.102

AC:

527

AN:

5152

South Asian (SAS)

AF:

0.175

AC:

846

AN:

4822

European-Finnish (FIN)

AF:

0.120

AC:

1278

AN:

10618

Middle Eastern (MID)

AF:

0.170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.118

AC:

7998

AN:

67966

Other (OTH)

AF:

0.189

AC:

400

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1164

2327

3491

4654

5818

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

330

660

990

1320

1650

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.166

Hom.:

5239

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

(source)

DANN

Benign

0.92

PhyloP100

-0.20

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over