rs2071570

Variant names:

• chr17-40100837-C-A
• rs2071570
• NM_021724.5:c.-743G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-40100837-C-A
• chr17-40100837-C-G
• chr17-40100837-C-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.-743G>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 189,340 control chromosomes in the GnomAD database, including 5,926 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 0.25 (4988 hom., cov: 33)
  • Exomes 𝑓: 0.20 (938 hom.)
• Consequence: NR1D1 NM_021724.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0830
• Publications: 18 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=-0.74).
• 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.-743G>T		upstream_gene_variant		ENST00000246672.4	NP_068370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR1D1	ENST00000246672.4	c.-743G>T		upstream_gene_variant		1	NM_021724.5	ENSP00000246672.3

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37264 AN: 152074 Hom.: 4980 Cov.: 33

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.216

GnomAD4 exome AF: 0.205 AC: 7614 AN: 37148 Hom.: 938 AF XY: 0.206 AC XY: 3820 AN XY: 18574

African (AFR) AF: 0.208 AC: 301 AN: 1448

American (AMR) AF: 0.131 AC: 127 AN: 968

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 329 AN: 1746

East Asian (EAS) AF: 0.420 AC: 1214 AN: 2890

South Asian (SAS) AF: 0.135 AC: 47 AN: 348

European-Finnish (FIN) AF: 0.261 AC: 535 AN: 2048

Middle Eastern (MID) AF: 0.180 AC: 44 AN: 244

European-Non Finnish (NFE) AF: 0.181 AC: 4479 AN: 24800

Other (OTH) AF: 0.203 AC: 538 AN: 2656

GnomAD4 genome AF: 0.245 AC: 37306 AN: 152192 Hom.: 4988 Cov.: 33 AF XY: 0.245 AC XY: 18226 AN XY: 74400

African (AFR) AF: 0.257 AC: 10683 AN: 41544

American (AMR) AF: 0.192 AC: 2940 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 820 AN: 3468

East Asian (EAS) AF: 0.529 AC: 2730 AN: 5156

South Asian (SAS) AF: 0.190 AC: 917 AN: 4824

European-Finnish (FIN) AF: 0.313 AC: 3318 AN: 10600

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.226 AC: 15335 AN: 67984

Other (OTH) AF: 0.215 AC: 455 AN: 2112

Alfa AF: 0.227 Hom.: 17945

Bravo AF: 0.238

Asia WGS AF: 0.341 AC: 1185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	3.1
DANN	Benign	0.79
PhyloP100		0.083
PromoterAI		-0.14	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2071570; hg19: chr17-38257090; COSMIC: COSV55857863;