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GeneBe

rs2859387

chr1-7827188-G-Achr1-7827188-G-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001377275.1(PER3):c.2259G>A(p.Pro753=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 1,610,900 control chromosomes in the GnomAD database, including 127,151 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.43 ( 14670 hom., cov: 32)
Exomes 𝑓: 0.38 ( 112481 hom. )

Consequence

PER3
NM_001377275.1 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.16
Variant links:
Genes affected
PER3 (HGNC:8847): (period circadian regulator 3) This gene is a member of the Period family of genes and is expressed in a circadian pattern in the suprachiasmatic nucleus, the primary circadian pacemaker in the mammalian brain. Genes in this family encode components of the circadian rhythms of locomotor activity, metabolism, and behavior. This gene is upregulated by CLOCK/ARNTL heterodimers but then represses this upregulation in a feedback loop using PER/CRY heterodimers to interact with CLOCK/ARNTL. Polymorphisms in this gene have been linked to sleep disorders. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2014]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-7827188-G-A is Benign according to our data. Variant chr1-7827188-G-A is described in ClinVar as [Benign]. Clinvar id is 3060684.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-3.16 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PER3NM_001377275.1 linkuse as main transcriptc.2259G>A p.Pro753= synonymous_variant 18/22 ENST00000377532.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PER3ENST00000377532.8 linkuse as main transcriptc.2259G>A p.Pro753= synonymous_variant 18/221 NM_001377275.1 A2P56645-2
ENST00000451646.1 linkuse as main transcriptn.155C>T non_coding_transcript_exon_variant 1/33

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.425
AC:
64596
AN:
151852
Hom.:
14662
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.517
Gnomad AMI
AF:
0.276
Gnomad AMR
AF:
0.450
Gnomad ASJ
AF:
0.314
Gnomad EAS
AF:
0.788
Gnomad SAS
AF:
0.383
Gnomad FIN
AF:
0.334
Gnomad MID
AF:
0.274
Gnomad NFE
AF:
0.363
Gnomad OTH
AF:
0.397
GnomAD3 exomes
AF:
0.430
AC:
105731
AN:
245866
Hom.:
25188
AF XY:
0.416
AC XY:
55698
AN XY:
133738
show subpopulations
Gnomad AFR exome
AF:
0.519
Gnomad AMR exome
AF:
0.565
Gnomad ASJ exome
AF:
0.320
Gnomad EAS exome
AF:
0.811
Gnomad SAS exome
AF:
0.365
Gnomad FIN exome
AF:
0.344
Gnomad NFE exome
AF:
0.360
Gnomad OTH exome
AF:
0.388
GnomAD4 exome
AF:
0.384
AC:
560026
AN:
1458930
Hom.:
112481
Cov.:
44
AF XY:
0.380
AC XY:
275859
AN XY:
725436
show subpopulations
Gnomad4 AFR exome
AF:
0.521
Gnomad4 AMR exome
AF:
0.552
Gnomad4 ASJ exome
AF:
0.323
Gnomad4 EAS exome
AF:
0.759
Gnomad4 SAS exome
AF:
0.370
Gnomad4 FIN exome
AF:
0.349
Gnomad4 NFE exome
AF:
0.363
Gnomad4 OTH exome
AF:
0.400
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.425
AC:
64652
AN:
151970
Hom.:
14670
Cov.:
32
AF XY:
0.424
AC XY:
31477
AN XY:
74270
show subpopulations
Gnomad4 AFR
AF:
0.517
Gnomad4 AMR
AF:
0.450
Gnomad4 ASJ
AF:
0.314
Gnomad4 EAS
AF:
0.788
Gnomad4 SAS
AF:
0.382
Gnomad4 FIN
AF:
0.334
Gnomad4 NFE
AF:
0.363
Gnomad4 OTH
AF:
0.395
Alfa
AF:
0.354
Hom.:
2860
Bravo
AF:
0.442
Asia WGS
AF:
0.576
AC:
2002
AN:
3478
EpiCase
AF:
0.353
EpiControl
AF:
0.355

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

PER3-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 17, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
Cadd
Benign
0.019
Dann
Benign
0.88

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: rs2859387; hg19: chr1-7887248; COSMIC: COSV62707524; API