17-40095540-G-A

Variant names:

• chr17-40095540-G-A
• rs193074453
• NM_021724.5:c.1152C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_021724.5(NR1D1):​c.1152C>T​(p.Asn384Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000758 in 1,451,420 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000076 (0 hom.)
• Consequence: NR1D1 NM_021724.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.33
• Publications: 0 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP7: Synonymous conserved (PhyloP=-4.33 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR1D1	NM_021724.5	c.1152C>T	p.Asn384Asn	synonymous_variant	Exon 5 of 8	ENST00000246672.4	NP_068370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR1D1	ENST00000246672.4	c.1152C>T	p.Asn384Asn	synonymous_variant	Exon 5 of 8	1	NM_021724.5	ENSP00000246672.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000164 AC: 4 AN: 243190 AF XY: 0.0000152

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000597

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000110

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000758 AC: 11 AN: 1451420 Hom.: 0 Cov.: 37 AF XY: 0.0000111 AC XY: 8 AN XY: 720946

African (AFR) AF: 0.00 AC: 0 AN: 33246

American (AMR) AF: 0.0000458 AC: 2 AN: 43676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25360

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39540

South Asian (SAS) AF: 0.0000236 AC: 2 AN: 84830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53062

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00000542 AC: 6 AN: 1106092

Other (OTH) AF: 0.00 AC: 0 AN: 59916

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.14
DANN	Benign	0.81
PhyloP100		-4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs193074453; hg19: chr17-38251793;