3-23956113-C-T

Variant names:

• chr3-23956113-C-T
• rs61732085
• NM_005126.5:c.360C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_005126.5(NR1D2):​c.360C>T​(p.Cys120Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00533 in 1,612,538 control chromosomes in the GnomAD database, including 399 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (211 hom., cov: 33)
  • Exomes 𝑓: 0.0031 (188 hom.)
• Consequence: NR1D2 NM_005126.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.43
• Publications: 4 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: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 3-23956113-C-T is Benign according to our data. Variant chr3-23956113-C-T is described in ClinVar as Benign. ClinVar VariationId is 775851.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.43 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0911 is higher than 0.05.

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.360C>T	p.Cys120Cys	synonymous	Exon 3 of 8	NP_005117.3
	NR1D2	NM_001145425.2		c.135C>T	p.Cys45Cys	synonymous	Exon 3 of 8	NP_001138897.1	B4DXD3
	NR1D2	NR_110524.2		n.653C>T		non_coding_transcript_exon	Exon 3 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR1D2	ENST00000312521.9	TSL:1 MANE Select	c.360C>T	p.Cys120Cys	synonymous	Exon 3 of 8	ENSP00000310006.3	Q14995
	NR1D2	ENST00000383773.8	TSL:1	n.360C>T		non_coding_transcript_exon	Exon 3 of 9	ENSP00000373283.3	Q6NSM0
	NR1D2	ENST00000947380.1		c.360C>T	p.Cys120Cys	synonymous	Exon 3 of 7	ENSP00000617439.1

Frequencies

GnomAD3 genomes AF: 0.0271 AC: 4121 AN: 152036 Hom.: 211 Cov.: 33

Gnomad AFR AF: 0.0938

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0104

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000823

Gnomad OTH AF: 0.0129

GnomAD2 exomes AF: 0.00752 AC: 1891 AN: 251460 AF XY: 0.00558

Gnomad AFR exome AF: 0.0984

Gnomad AMR exome AF: 0.00532

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000615

Gnomad OTH exome AF: 0.00489

GnomAD4 exome AF: 0.00306 AC: 4475 AN: 1460384 Hom.: 188 Cov.: 29 AF XY: 0.00269 AC XY: 1955 AN XY: 726602

African (AFR) AF: 0.0973 AC: 3252 AN: 33410

American (AMR) AF: 0.00613 AC: 274 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.000209 AC: 18 AN: 86230

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53400

Middle Eastern (MID) AF: 0.00660 AC: 38 AN: 5760

European-Non Finnish (NFE) AF: 0.000468 AC: 520 AN: 1110752

Other (OTH) AF: 0.00617 AC: 372 AN: 60318

GnomAD4 genome AF: 0.0271 AC: 4125 AN: 152154 Hom.: 211 Cov.: 33 AF XY: 0.0265 AC XY: 1972 AN XY: 74390

African (AFR) AF: 0.0936 AC: 3881 AN: 41476

American (AMR) AF: 0.0103 AC: 158 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000823 AC: 56 AN: 68022

Other (OTH) AF: 0.0128 AC: 27 AN: 2112

Alfa AF: 0.0220 Hom.: 169

Bravo AF: 0.0314

Asia WGS AF: 0.00606 AC: 21 AN: 3478

EpiCase AF: 0.000818

EpiControl AF: 0.00101

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	12
DANN	Benign	0.53
PhyloP100		1.4
Mutation Taster		=99/1	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: rs61732085; hg19: chr3-23997604; COSMIC: COSV104614861;