3-23956113-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

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

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.43
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NR1D2NM_005126.5 linkc.360C>T p.Cys120Cys synonymous_variant Exon 3 of 8 ENST00000312521.9 NP_005117.3 Q14995F1D8P2
NR1D2NM_001145425.2 linkc.135C>T p.Cys45Cys synonymous_variant Exon 3 of 8 NP_001138897.1 B4DXD3
NR1D2XM_006713451.4 linkc.360C>T p.Cys120Cys synonymous_variant Exon 3 of 7 XP_006713514.1
NR1D2NR_110524.2 linkn.653C>T non_coding_transcript_exon_variant Exon 3 of 9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NR1D2ENST00000312521.9 linkc.360C>T p.Cys120Cys synonymous_variant Exon 3 of 8 1 NM_005126.5 ENSP00000310006.3 Q14995
NR1D2ENST00000383773.8 linkn.360C>T non_coding_transcript_exon_variant Exon 3 of 9 1 ENSP00000373283.3 Q6NSM0
NR1D2ENST00000468700.1 linkn.255C>T non_coding_transcript_exon_variant Exon 2 of 4 3
NR1D2ENST00000492552.5 linkn.477C>T non_coding_transcript_exon_variant Exon 3 of 8 2 ENSP00000520893.1

Frequencies

GnomAD3 genomes
AF:
0.0271
AC:
4121
AN:
152036
Hom.:
211
Cov.:
33
show subpopulations
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
GnomAD3 exomes
AF:
0.00752
AC:
1891
AN:
251460
Hom.:
85
AF XY:
0.00558
AC XY:
759
AN XY:
135900
show subpopulations
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 SAS exome
AF:
0.000196
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
show subpopulations
Gnomad4 AFR exome
AF:
0.0973
Gnomad4 AMR exome
AF:
0.00613
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000209
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.000468
Gnomad4 OTH exome
AF:
0.00617
GnomAD4 genome
AF:
0.0271
AC:
4125
AN:
152154
Hom.:
211
Cov.:
33
AF XY:
0.0265
AC XY:
1972
AN XY:
74390
show subpopulations
Gnomad4 AFR
AF:
0.0936
Gnomad4 AMR
AF:
0.0103
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000621
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000823
Gnomad4 OTH
AF:
0.0128
Alfa
AF:
0.0122
Hom.:
48
Bravo
AF:
0.0314
Asia WGS
AF:
0.00606
AC:
21
AN:
3478
EpiCase
AF:
0.000818
EpiControl
AF:
0.00101

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Dec 31, 2019
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.36
CADD
Benign
12
DANN
Benign
0.53

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs61732085; hg19: chr3-23997604; COSMIC: COSV104614861; API