Genetic Variant PER1:c.1388+13T>C (chr17-8147661-A-G) – 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.1388+13T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.071 in 1,613,792 control chromosomes in the GnomAD database, including 8,706 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 0.099 ( 1242 hom., cov: 33)

Exomes 𝑓: 0.068 ( 7464 hom. )

Consequence

PER1
NM_002616.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.37

Publications

23 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=-0.75).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PER1	NM_002616.3 link	c.1388+13T>C		intron_variant	Intron 11 of 22	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.1388+13T>C		intron_variant	Intron 11 of 22	1	NM_002616.3	ENSP00000314420.4		O15534-1

Frequencies

GnomAD3 genomes

AF:

0.0988

AC:

15022

AN:

152118

Hom.:

1231

Cov.:

show subpopulations

Gnomad AFR

AF:

0.122

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.250

Gnomad ASJ

AF:

0.102

Gnomad EAS

AF:

0.239

Gnomad SAS

AF:

0.129

Gnomad FIN

AF:

0.0399

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0479

Gnomad OTH

AF:

0.0982

GnomAD2 exomes

AF:

0.123

AC:

30875

AN:

250524

AF XY:

0.112

show subpopulations

Gnomad AFR exome

AF:

0.124

Gnomad AMR exome

AF:

0.393

Gnomad ASJ exome

AF:

0.105

Gnomad EAS exome

AF:

0.225

Gnomad FIN exome

AF:

0.0370

Gnomad NFE exome

AF:

0.0447

Gnomad OTH exome

AF:

0.102

GnomAD4 exome

AF:

0.0681

AC:

99490

AN:

1461556

Hom.:

7464

Cov.:

AF XY:

0.0680

AC XY:

49425

AN XY:

727052

show subpopulations

African (AFR)

AF:

0.127

AC:

4239

AN:

33476

American (AMR)

AF:

0.377

AC:

16858

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.107

AC:

2787

AN:

26124

East Asian (EAS)

AF:

0.264

AC:

10490

AN:

39698

South Asian (SAS)

AF:

0.116

AC:

9984

AN:

86248

European-Finnish (FIN)

AF:

0.0351

AC:

1866

AN:

53196

Middle Eastern (MID)

AF:

0.0803

AC:

463

AN:

5768

European-Non Finnish (NFE)

AF:

0.0431

AC:

47926

AN:

1111956

Other (OTH)

AF:

0.0808

AC:

4877

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

5102

10204

15306

20408

25510

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2190

4380

6570

8760

10950

<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:

0.0989

AC:

15059

AN:

152236

Hom.:

1242

Cov.:

AF XY:

0.103

AC XY:

7689

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.122

AC:

5069

AN:

41530

American (AMR)

AF:

0.251

AC:

3834

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.102

AC:

354

AN:

3472

East Asian (EAS)

AF:

0.240

AC:

1237

AN:

5164

South Asian (SAS)

AF:

0.129

AC:

621

AN:

4832

European-Finnish (FIN)

AF:

0.0399

AC:

424

AN:

10622

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0479

AC:

3260

AN:

68000

Other (OTH)

AF:

0.104

AC:

220

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

658

1316

1975

2633

3291

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

312

468

624

780

<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:

0.0702

Hom.:

3193

Bravo

AF:

0.116

Asia WGS

AF:

0.196

AC:

680

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

9.2

(source)

DANN

Benign

0.71

PhyloP100

1.4

Mutation Taster

=100/0

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