dbSNP rs2585408: PER1:c.*633G>A (chr17-8140435-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002616.3(PER1):c.*633G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 189,024 control chromosomes in the GnomAD database, including 13,029 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 0.36 ( 10573 hom., cov: 33)

Exomes 𝑓: 0.34 ( 2456 hom. )

Consequence

PER1
NM_002616.3 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.728

Publications

16 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002616.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PER1	NM_002616.3	MANE Select	c.*633G>A		downstream_gene	N/A	NP_002607.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PER1	ENST00000317276.9	TSL:1 MANE Select	c.*633G>A	downstream_gene	N/A	ENSP00000314420.4
PER1	ENST00000857860.1		c.*633G>A	downstream_gene	N/A	ENSP00000527919.1
PER1	ENST00000857861.1		c.*633G>A	downstream_gene	N/A	ENSP00000527920.1

Frequencies

GnomAD3 genomes

AF:

0.364

AC:

55319

AN:

152060

Hom.:

10574

Cov.:

show subpopulations

Gnomad AFR

AF:

0.328

Gnomad AMI

AF:

0.400

Gnomad AMR

AF:

0.274

Gnomad ASJ

AF:

0.293

Gnomad EAS

AF:

0.115

Gnomad SAS

AF:

0.232

Gnomad FIN

AF:

0.467

Gnomad MID

AF:

0.313

Gnomad NFE

AF:

0.421

Gnomad OTH

AF:

0.360

GnomAD4 exome

AF:

0.342

AC:

12609

AN:

36846

Hom.:

2456

Cov.:

AF XY:

0.343

AC XY:

5883

AN XY:

17144

show subpopulations

African (AFR)

AF:

0.337

AC:

478

AN:

1420

American (AMR)

AF:

0.236

AC:

213

AN:

904

Ashkenazi Jewish (ASJ)

AF:

0.304

AC:

696

AN:

2292

East Asian (EAS)

AF:

0.137

AC:

929

AN:

6790

South Asian (SAS)

AF:

0.256

AC:

AN:

324

European-Finnish (FIN)

AF:

0.468

AC:

AN:

154

Middle Eastern (MID)

AF:

0.284

AC:

AN:

208

European-Non Finnish (NFE)

AF:

0.414

AC:

8995

AN:

21704

Other (OTH)

AF:

0.355

AC:

1084

AN:

3050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

390

781

1171

1562

1952

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

144

180

<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:

0.364

AC:

55328

AN:

152178

Hom.:

10573

Cov.:

AF XY:

0.359

AC XY:

26736

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.328

AC:

13598

AN:

41500

American (AMR)

AF:

0.273

AC:

4181

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.293

AC:

1018

AN:

3470

East Asian (EAS)

AF:

0.115

AC:

599

AN:

5188

South Asian (SAS)

AF:

0.232

AC:

1120

AN:

4830

European-Finnish (FIN)

AF:

0.467

AC:

4947

AN:

10584

Middle Eastern (MID)

AF:

0.320

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.421

AC:

28655

AN:

67994

Other (OTH)

AF:

0.355

AC:

751

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1792

3584

5375

7167

8959

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

526

1052

1578

2104

2630

<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:

0.393

Hom.:

20327

Bravo

AF:

0.347

Asia WGS

AF:

0.178

AC:

624

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.6

(source)

DANN

Benign

0.58

PhyloP100

-0.73

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over