dbSNP rs939347: NR1D1:c.-346C>T (chr17-40100440-G-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.-346C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 458,460 control chromosomes in the GnomAD database, including 18,387 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 0.28 ( 6702 hom., cov: 33)

Exomes 𝑓: 0.26 ( 11685 hom. )

Consequence

NR1D1
NM_021724.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.11

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=-0.68).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR1D1	NM_021724.5 link	c.-346C>T		5_prime_UTR_variant	Exon 1 of 8	ENST00000246672.4	NP_068370.1	P20393F1D8S3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR1D1	ENST00000246672.4 link	c.-346C>T		5_prime_UTR_variant	Exon 1 of 8	1	NM_021724.5	ENSP00000246672.3		P20393

Frequencies

GnomAD3 genomes

AF:

0.285

AC:

43292

AN:

152092

Hom.:

6691

Cov.:

show subpopulations

Gnomad AFR

AF:

0.354

Gnomad AMI

AF:

0.0910

Gnomad AMR

AF:

0.219

Gnomad ASJ

AF:

0.220

Gnomad EAS

AF:

0.532

Gnomad SAS

AF:

0.182

Gnomad FIN

AF:

0.336

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.245

Gnomad OTH

AF:

0.251

GnomAD4 exome

AF:

0.259

AC:

79468

AN:

306248

Hom.:

11685

Cov.:

AF XY:

0.255

AC XY:

40509

AN XY:

158786

show subpopulations

African (AFR)

AF:

0.349

AC:

3055

AN:

8748

American (AMR)

AF:

0.204

AC:

2157

AN:

10552

Ashkenazi Jewish (ASJ)

AF:

0.213

AC:

2201

AN:

10340

East Asian (EAS)

AF:

0.488

AC:

12061

AN:

24690

South Asian (SAS)

AF:

0.159

AC:

2771

AN:

17456

European-Finnish (FIN)

AF:

0.313

AC:

7279

AN:

23224

Middle Eastern (MID)

AF:

0.190

AC:

283

AN:

1490

European-Non Finnish (NFE)

AF:

0.234

AC:

44633

AN:

190686

Other (OTH)

AF:

0.264

AC:

5028

AN:

19062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

3070

6139

9209

12278

15348

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.285

AC:

43344

AN:

152212

Hom.:

6702

Cov.:

AF XY:

0.285

AC XY:

21181

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.354

AC:

14714

AN:

41530

American (AMR)

AF:

0.220

AC:

3365

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.220

AC:

764

AN:

3470

East Asian (EAS)

AF:

0.531

AC:

2750

AN:

5178

South Asian (SAS)

AF:

0.182

AC:

879

AN:

4826

European-Finnish (FIN)

AF:

0.336

AC:

3555

AN:

10596

Middle Eastern (MID)

AF:

0.204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.245

AC:

16646

AN:

67994

Other (OTH)

AF:

0.250

AC:

528

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1558

3116

4674

6232

7790

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.257

Hom.:

10298

Bravo

AF:

0.281

Asia WGS

AF:

0.342

AC:

1190

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.89

PhyloP100

1.1

PromoterAI

-0.080

Neutral

(source)

Mutation Taster

=299/1

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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rs939347

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over