rs12941497

Positions:

• chr17-40099341-G-A
• chr17-40099341-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.31+723C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 152,130 control chromosomes in the GnomAD database, including 9,177 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 0.33 (9177 hom., cov: 32)
• Consequence: NR1D1 NM_021724.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.591

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR1D1	NM_021724.5	c.31+723C>T		intron_variant		ENST00000246672.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR1D1	ENST00000246672.4	c.31+723C>T		intron_variant		1	NM_021724.5	P1

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50330 AN: 152012 Hom.: 9170 Cov.: 32

Gnomad AFR AF: 0.463

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.288

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.331 AC: 50378 AN: 152130 Hom.: 9177 Cov.: 32 AF XY: 0.330 AC XY: 24532 AN XY: 74372

Gnomad4 AFR AF: 0.462

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.530

Gnomad4 SAS AF: 0.189

Gnomad4 FIN AF: 0.348

Gnomad4 NFE AF: 0.271

Gnomad4 OTH AF: 0.286

Alfa AF: 0.259 Hom.: 7245

Bravo AF: 0.330

Asia WGS AF: 0.350 AC: 1217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	9.5
DANN	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs12941497; hg19: chr17-38255594;