Genetic Variant NR1D1:c.370+106G>A (chr17-40096959-C-T) – 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.370+106G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 1,287,204 control chromosomes in the GnomAD database, including 20,503 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 0.20 ( 3779 hom., cov: 33)

Exomes 𝑓: 0.15 ( 16724 hom. )

Consequence

NR1D1
NM_021724.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.883

Publications

59 publications found

Variant links:

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:

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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=-0.76).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.562 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.370+106G>A		intron	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.370+106G>A		intron	N/A	ENSP00000246672.3	P20393

Frequencies

GnomAD3 genomes

AF:

0.199

AC:

30317

AN:

152082

Hom.:

3773

Cov.:

show subpopulations

Gnomad AFR

AF:

0.275

Gnomad AMI

AF:

0.176

Gnomad AMR

AF:

0.223

Gnomad ASJ

AF:

0.147

Gnomad EAS

AF:

0.578

Gnomad SAS

AF:

0.145

Gnomad FIN

AF:

0.200

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.127

Gnomad OTH

AF:

0.177

GnomAD4 exome

AF:

0.150

AC:

170540

AN:

1135002

Hom.:

16724

Cov.:

AF XY:

0.149

AC XY:

84387

AN XY:

568206

show subpopulations

African (AFR)

AF:

0.279

AC:

7302

AN:

26142

American (AMR)

AF:

0.219

AC:

7519

AN:

34382

Ashkenazi Jewish (ASJ)

AF:

0.147

AC:

2875

AN:

19584

East Asian (EAS)

AF:

0.547

AC:

20690

AN:

37842

South Asian (SAS)

AF:

0.131

AC:

9047

AN:

69270

European-Finnish (FIN)

AF:

0.180

AC:

8405

AN:

46660

Middle Eastern (MID)

AF:

0.146

AC:

589

AN:

4036

European-Non Finnish (NFE)

AF:

0.125

AC:

105681

AN:

848432

Other (OTH)

AF:

0.173

AC:

8432

AN:

48654

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

7277

14553

21830

29106

36383

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3820

7640

11460

15280

19100

<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:

0.199

AC:

30361

AN:

152202

Hom.:

3779

Cov.:

AF XY:

0.204

AC XY:

15199

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.275

AC:

11400

AN:

41494

American (AMR)

AF:

0.224

AC:

3421

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.147

AC:

510

AN:

3472

East Asian (EAS)

AF:

0.579

AC:

2997

AN:

5178

South Asian (SAS)

AF:

0.146

AC:

703

AN:

4824

European-Finnish (FIN)

AF:

0.200

AC:

2126

AN:

10608

Middle Eastern (MID)

AF:

0.173

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.127

AC:

8622

AN:

68014

Other (OTH)

AF:

0.175

AC:

371

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1205

2409

3614

4818

6023

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

308

616

924

1232

1540

<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:

0.152

Hom.:

6689

Bravo

AF:

0.206

Asia WGS

AF:

0.319

AC:

1108

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

8.0

(source)

DANN

Benign

0.61

PhyloP100

0.88

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over