dbSNP rs3027178: PER1:p.Thr213Thr (chr17-8149767-T-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_002616.3(PER1):c.639A>C(p.Thr213Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 1,612,592 control chromosomes in the GnomAD database, including 70,256 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 0.29 ( 6477 hom., cov: 32)

Exomes 𝑓: 0.29 ( 63779 hom. )

Consequence

PER1
NM_002616.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.13

Publications

43 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP7

Synonymous conserved (PhyloP=-5.13 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PER1	NM_002616.3 link	c.639A>C	p.Thr213Thr	synonymous_variant	Exon 5 of 23	ENST00000317276.9	NP_002607.2	O15534-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PER1	ENST00000317276.9 link	c.639A>C	p.Thr213Thr	synonymous_variant	Exon 5 of 23	1	NM_002616.3	ENSP00000314420.4		O15534-1

Frequencies

GnomAD3 genomes

AF:

0.288

AC:

43729

AN:

151934

Hom.:

6467

Cov.:

show subpopulations

Gnomad AFR

AF:

0.255

Gnomad AMI

AF:

0.246

Gnomad AMR

AF:

0.413

Gnomad ASJ

AF:

0.328

Gnomad EAS

AF:

0.291

Gnomad SAS

AF:

0.201

Gnomad FIN

AF:

0.228

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.293

Gnomad OTH

AF:

0.287

GnomAD2 exomes

AF:

0.303

AC:

75731

AN:

250034

AF XY:

0.295

show subpopulations

Gnomad AFR exome

AF:

0.257

Gnomad AMR exome

AF:

0.505

Gnomad ASJ exome

AF:

0.329

Gnomad EAS exome

AF:

0.274

Gnomad FIN exome

AF:

0.235

Gnomad NFE exome

AF:

0.288

Gnomad OTH exome

AF:

0.308

GnomAD4 exome

AF:

0.291

AC:

425263

AN:

1460540

Hom.:

63779

Cov.:

AF XY:

0.288

AC XY:

209561

AN XY:

726578

show subpopulations

African (AFR)

AF:

0.253

AC:

8475

AN:

33478

American (AMR)

AF:

0.496

AC:

22167

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.332

AC:

8682

AN:

26134

East Asian (EAS)

AF:

0.304

AC:

12055

AN:

39700

South Asian (SAS)

AF:

0.210

AC:

18134

AN:

86256

European-Finnish (FIN)

AF:

0.232

AC:

12113

AN:

52154

Middle Eastern (MID)

AF:

0.299

AC:

1726

AN:

5768

European-Non Finnish (NFE)

AF:

0.292

AC:

324484

AN:

1111946

Other (OTH)

AF:

0.289

AC:

17427

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

18316

36632

54948

73264

91580

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10898

21796

32694

43592

54490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.288

AC:

43765

AN:

152052

Hom.:

6477

Cov.:

AF XY:

0.286

AC XY:

21283

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.255

AC:

10567

AN:

41468

American (AMR)

AF:

0.413

AC:

6310

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.328

AC:

1137

AN:

3470

East Asian (EAS)

AF:

0.291

AC:

1502

AN:

5170

South Asian (SAS)

AF:

0.201

AC:

971

AN:

4828

European-Finnish (FIN)

AF:

0.228

AC:

2409

AN:

10586

Middle Eastern (MID)

AF:

0.344

AC:

101

AN:

294

European-Non Finnish (NFE)

AF:

0.293

AC:

19933

AN:

67944

Other (OTH)

AF:

0.290

AC:

612

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1617

3233

4850

6466

8083

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

434

868

1302

1736

2170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.293

Hom.:

3536

Bravo

AF:

0.304

Asia WGS

AF:

0.245

AC:

851

AN:

3478

EpiCase

AF:

0.307

EpiControl

AF:

0.302

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.045

(source)

DANN

Benign

0.60

PhyloP100

-5.1

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over