chr17-40098239-C-T

Variant names:

• chr17-40098239-C-T
• rs2071427
• NM_021724.5:c.32-836G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_021724.5(NR1D1):​c.32-836G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 152,054 control chromosomes in the GnomAD database, including 16,284 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 0.42 (16284 hom., cov: 32)
• Consequence: NR1D1 NM_021724.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.879
• Publications: 47 publications found

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.721 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.32-836G>A		intron	N/A	NP_068370.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR1D1	ENST00000246672.4	TSL:1 MANE Select	c.32-836G>A		intron	N/A	ENSP00000246672.3

Frequencies

GnomAD3 genomes AF: 0.415 AC: 63000 AN: 151934 Hom.: 16236 Cov.: 32

Gnomad AFR AF: 0.728

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.552

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.361

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

GnomAD4 genome AF: 0.415 AC: 63116 AN: 152054 Hom.: 16284 Cov.: 32 AF XY: 0.413 AC XY: 30684 AN XY: 74336

African (AFR) AF: 0.728 AC: 30192 AN: 41480

American (AMR) AF: 0.328 AC: 5014 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 929 AN: 3470

East Asian (EAS) AF: 0.551 AC: 2849 AN: 5166

South Asian (SAS) AF: 0.208 AC: 1003 AN: 4830

European-Finnish (FIN) AF: 0.338 AC: 3568 AN: 10558

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.271 AC: 18441 AN: 67956

Other (OTH) AF: 0.359 AC: 757 AN: 2110

Alfa AF: 0.318 Hom.: 31866

Bravo AF: 0.429

Asia WGS AF: 0.389 AC: 1349 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	17
DANN	Benign	0.76
PhyloP100		0.88
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2071427; hg19: chr17-38254492;