chr17-40099341-G-A

Variant names:

• chr17-40099341-G-A
• rs12941497
• NM_021724.5:c.31+723C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 23 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 -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 rank	MANE	Protein	UniProt
NR1D1	NM_021724.5	c.31+723C>T		intron_variant	Intron 1 of 7	ENST00000246672.4	NP_068370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR1D1	ENST00000246672.4	c.31+723C>T		intron_variant	Intron 1 of 7	1	NM_021724.5	ENSP00000246672.3

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

African (AFR) AF: 0.462 AC: 19186 AN: 41498

American (AMR) AF: 0.246 AC: 3769 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 940 AN: 3472

East Asian (EAS) AF: 0.530 AC: 2729 AN: 5152

South Asian (SAS) AF: 0.189 AC: 913 AN: 4824

European-Finnish (FIN) AF: 0.348 AC: 3676 AN: 10576

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.271 AC: 18400 AN: 67992

Other (OTH) AF: 0.286 AC: 603 AN: 2108

Alfa AF: 0.282 Hom.: 13739

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
PhyloP100		0.59
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12941497; hg19: chr17-38255594;