Variant rs2253820 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_002616.3(PER1):c.2361A>G(p.Thr787=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 1,581,704 control chromosomes in the GnomAD database, including 516,872 homozygotes. 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: 𝑓 0.71 ( 40428 hom., cov: 32)

Exomes 𝑓: 0.81 ( 476444 hom. )

Consequence

PER1
NM_002616.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.14

Variant links:

Genes affected

PER1 (HGNC:8845): (period circadian regulator 1) 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 may increase the risk of getting certain cancers. Alternative splicing has been observed in this gene; however, these variants have not been fully described. [provided by RefSeq, Jan 2014]

PER1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP7

Synonymous conserved (PhyloP=-3.14 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PER1	NM_002616.3 linkuse as main transcript	c.2361A>G	p.Thr787=	synonymous_variant	18/23	ENST00000317276.9	NP_002607.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PER1	ENST00000317276.9 linkuse as main transcript	c.2361A>G	p.Thr787=	synonymous_variant	18/23	1	NM_002616.3	ENSP00000314420	P1	O15534-1

Frequencies

GnomAD3 genomes

AF:

0.712

AC:

108223

AN:

151898

Hom.:

40427

Cov.:

show subpopulations

Gnomad AFR

AF:

0.561

Gnomad AMI

AF:

0.826

Gnomad AMR

AF:

0.577

Gnomad ASJ

AF:

0.598

Gnomad EAS

AF:

0.306

Gnomad SAS

AF:

0.765

Gnomad FIN

AF:

0.862

Gnomad MID

AF:

0.620

Gnomad NFE

AF:

0.844

Gnomad OTH

AF:

0.696

GnomAD3 exomes

AF:

0.699

AC:

148567

AN:

212502

Hom.:

56197

AF XY:

0.720

AC XY:

82742

AN XY:

114916

show subpopulations

Gnomad AFR exome

AF:

0.541

Gnomad AMR exome

AF:

0.423

Gnomad ASJ exome

AF:

0.603

Gnomad EAS exome

AF:

0.295

Gnomad SAS exome

AF:

0.765

Gnomad FIN exome

AF:

0.858

Gnomad NFE exome

AF:

0.841

Gnomad OTH exome

AF:

0.731

GnomAD4 exome

AF:

0.806

AC:

1152247

AN:

1429688

Hom.:

476444

Cov.:

AF XY:

0.807

AC XY:

571466

AN XY:

708558

show subpopulations

Gnomad4 AFR exome

AF:

0.548

Gnomad4 AMR exome

AF:

0.443

Gnomad4 ASJ exome

AF:

0.607

Gnomad4 EAS exome

AF:

0.292

Gnomad4 SAS exome

AF:

0.771

Gnomad4 FIN exome

AF:

0.869

Gnomad4 NFE exome

AF:

0.853

Gnomad4 OTH exome

AF:

0.758

GnomAD4 genome

AF:

0.712

AC:

108260

AN:

152016

Hom.:

40428

Cov.:

AF XY:

0.710

AC XY:

52729

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.561

Gnomad4 AMR

AF:

0.576

Gnomad4 ASJ

AF:

0.598

Gnomad4 EAS

AF:

0.306

Gnomad4 SAS

AF:

0.766

Gnomad4 FIN

AF:

0.862

Gnomad4 NFE

AF:

0.844

Gnomad4 OTH

AF:

0.687

Alfa

AF:

0.795

Hom.:

68671

Bravo

AF:

0.679

Asia WGS

AF:

0.540

AC:

1880

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.60

DANN

Benign

0.76

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over