rs939347

chr17-40100440-G-Achr17-40100440-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
NR1D1	NM_021724.5	c.-346C>T		5_prime_UTR_variant	1/8	ENST00000246672.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR1D1	ENST00000246672.4	c.-346C>T		5_prime_UTR_variant	1/8	1	NM_021724.5	P1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43292 AN: 152092 Hom.: 6691 Cov.: 33

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.: 0 AF XY: 0.255 AC XY: 40509 AN XY: 158786

Gnomad4 AFR exome AF: 0.349

Gnomad4 AMR exome AF: 0.204

Gnomad4 ASJ exome AF: 0.213

Gnomad4 EAS exome AF: 0.488

Gnomad4 SAS exome AF: 0.159

Gnomad4 FIN exome AF: 0.313

Gnomad4 NFE exome AF: 0.234

Gnomad4 OTH exome AF: 0.264

GnomAD4 genome AF: 0.285 AC: 43344 AN: 152212 Hom.: 6702 Cov.: 33 AF XY: 0.285 AC XY: 21181 AN XY: 74424

Gnomad4 AFR AF: 0.354

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.531

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.336

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.250

Alfa AF: 0.249 Hom.: 2808

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	16
Dann	Benign	0.89

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

LitVar

Other links and lift over

dbSNP: rs939347; hg19: chr17-38256693; COSMIC: COSV55859846;