rs1358487339

Variant names:

• chr3-23961982-C-A
• rs1358487339
• NM_005126.5:c.523C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-23961982-C-A
• chr3-23961982-C-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_005126.5(NR1D2):​c.523C>A​(p.Arg175Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000695 in 1,439,130 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: 6.9e-7 (0 hom.)
• Consequence: NR1D2 NM_005126.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.92
• Publications: 0 publications found

Genes affected

NR1D2 (HGNC:7963): (nuclear receptor subfamily 1 group D member 2) This gene encodes a member of the nuclear hormone receptor family, specifically the NR1 subfamily of receptors. The encoded protein functions as a transcriptional repressor and may play a role in circadian rhythms and carbohydrate and lipid metabolism. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP7: Synonymous conserved (PhyloP=2.92 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005126.5. 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
	NR1D2	NM_005126.5	MANE Select	c.523C>A	p.Arg175Arg	synonymous	Exon 5 of 8	NP_005117.3
	NR1D2	NM_001145425.2		c.298C>A	p.Arg100Arg	synonymous	Exon 5 of 8	NP_001138897.1	B4DXD3
	NR1D2	NR_110524.2		n.816C>A		non_coding_transcript_exon	Exon 5 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR1D2	ENST00000312521.9	TSL:1 MANE Select	c.523C>A	p.Arg175Arg	synonymous	Exon 5 of 8	ENSP00000310006.3	Q14995
	NR1D2	ENST00000383773.8	TSL:1	n.523C>A		non_coding_transcript_exon	Exon 5 of 9	ENSP00000373283.3	Q6NSM0
	NR1D2	ENST00000947380.1		c.523C>A	p.Arg175Arg	synonymous	Exon 5 of 7	ENSP00000617439.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.95e-7 AC: 1 AN: 1439130 Hom.: 0 Cov.: 32 AF XY: 0.00000140 AC XY: 1 AN XY: 713606

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32426

American (AMR) AF: 0.00 AC: 0 AN: 40506

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24874

East Asian (EAS) AF: 0.00 AC: 0 AN: 39386

South Asian (SAS) AF: 0.0000119 AC: 1 AN: 83960

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52876

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5658

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1100120

Other (OTH) AF: 0.00 AC: 0 AN: 59324

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	13
DANN	Benign	0.82
PhyloP100		2.9

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1358487339; hg19: chr3-24003473;