dbSNP rs2071570: NR1D1:c.-743G>T (chr17-40100837-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021724.5(NR1D1):c.-743G>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 189,340 control chromosomes in the GnomAD database, including 5,926 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 0.25 ( 4988 hom., cov: 33)

Exomes 𝑓: 0.20 ( 938 hom. )

Consequence

NR1D1
NM_021724.5 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0830

Publications

18 publications found

Variant links:

COSMIC-nc: COSV55857863

Genes affected

NR1D1 (HGNC:7962): (nuclear receptor subfamily 1 group D member 1) This gene encodes a transcription factor that is a member of the nuclear receptor subfamily 1. The encoded protein is a ligand-sensitive transcription factor that negatively regulates the expression of core clock proteins. In particular this protein represses the circadian clock transcription factor aryl hydrocarbon receptor nuclear translocator-like protein 1 (ARNTL). This protein may also be involved in regulating genes that function in metabolic, inflammatory and cardiovascular processes. [provided by RefSeq, Jan 2013]

NR1D1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021724.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR1D1	NM_021724.5	MANE Select	c.-743G>T		upstream_gene	N/A	NP_068370.1	P20393

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR1D1	ENST00000246672.4	TSL:1 MANE Select	c.-743G>T		upstream_gene	N/A	ENSP00000246672.3	P20393

Frequencies

GnomAD3 genomes

AF:

0.245

AC:

37264

AN:

152074

Hom.:

4980

Cov.:

show subpopulations

Gnomad AFR

AF:

0.257

Gnomad AMI

AF:

0.0515

Gnomad AMR

AF:

0.192

Gnomad ASJ

AF:

0.236

Gnomad EAS

AF:

0.530

Gnomad SAS

AF:

0.190

Gnomad FIN

AF:

0.313

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.226

Gnomad OTH

AF:

0.216

GnomAD4 exome

AF:

0.205

AC:

7614

AN:

37148

Hom.:

938

AF XY:

0.206

AC XY:

3820

AN XY:

18574

show subpopulations

African (AFR)

AF:

0.208

AC:

301

AN:

1448

American (AMR)

AF:

0.131

AC:

127

AN:

968

Ashkenazi Jewish (ASJ)

AF:

0.188

AC:

329

AN:

1746

East Asian (EAS)

AF:

0.420

AC:

1214

AN:

2890

South Asian (SAS)

AF:

0.135

AC:

AN:

348

European-Finnish (FIN)

AF:

0.261

AC:

535

AN:

2048

Middle Eastern (MID)

AF:

0.180

AC:

AN:

244

European-Non Finnish (NFE)

AF:

0.181

AC:

4479

AN:

24800

Other (OTH)

AF:

0.203

AC:

538

AN:

2656

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

288

577

865

1154

1442

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

176

220

<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:

0.245

AC:

37306

AN:

152192

Hom.:

4988

Cov.:

AF XY:

0.245

AC XY:

18226

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.257

AC:

10683

AN:

41544

American (AMR)

AF:

0.192

AC:

2940

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.236

AC:

820

AN:

3468

East Asian (EAS)

AF:

0.529

AC:

2730

AN:

5156

South Asian (SAS)

AF:

0.190

AC:

917

AN:

4824

European-Finnish (FIN)

AF:

0.313

AC:

3318

AN:

10600

Middle Eastern (MID)

AF:

0.207

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.226

AC:

15335

AN:

67984

Other (OTH)

AF:

0.215

AC:

455

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1478

2955

4433

5910

7388

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

384

768

1152

1536

1920

<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:

0.227

Hom.:

17945

Bravo

AF:

0.238

Asia WGS

AF:

0.341

AC:

1185

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

3.1

(source)

DANN

Benign

0.79

PhyloP100

0.083

PromoterAI

-0.14

Neutral

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over