Genetic Variant PER1:c.1498-38C>G (chr17-8147419-G-C) – 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.1498-38C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 1,611,724 control chromosomes in the GnomAD database, including 146,524 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 0.45 ( 15919 hom., cov: 31)

Exomes 𝑓: 0.42 ( 130605 hom. )

Consequence

PER1
NM_002616.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.90

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=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PER1	NM_002616.3 link	c.1498-38C>G		intron_variant	Intron 12 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.1498-38C>G		intron_variant	Intron 12 of 22	1	NM_002616.3	ENSP00000314420.4		O15534-1

Frequencies

GnomAD3 genomes

AF:

0.445

AC:

67552

AN:

151774

Hom.:

15911

Cov.:

show subpopulations

Gnomad AFR

AF:

0.558

Gnomad AMI

AF:

0.401

Gnomad AMR

AF:

0.312

Gnomad ASJ

AF:

0.371

Gnomad EAS

AF:

0.118

Gnomad SAS

AF:

0.265

Gnomad FIN

AF:

0.504

Gnomad MID

AF:

0.370

Gnomad NFE

AF:

0.440

Gnomad OTH

AF:

0.422

GnomAD2 exomes

AF:

0.370

AC:

91478

AN:

247354

AF XY:

0.368

show subpopulations

Gnomad AFR exome

AF:

0.554

Gnomad AMR exome

AF:

0.205

Gnomad ASJ exome

AF:

0.373

Gnomad EAS exome

AF:

0.106

Gnomad FIN exome

AF:

0.498

Gnomad NFE exome

AF:

0.438

Gnomad OTH exome

AF:

0.379

GnomAD4 exome

AF:

0.415

AC:

605915

AN:

1459832

Hom.:

130605

Cov.:

AF XY:

0.411

AC XY:

298344

AN XY:

725964

show subpopulations

Gnomad4 AFR exome

AF:

0.559

AC:

18692

AN:

33462

Gnomad4 AMR exome

AF:

0.219

AC:

9787

AN:

44614

Gnomad4 ASJ exome

AF:

0.373

AC:

9735

AN:

26074

Gnomad4 EAS exome

AF:

0.129

AC:

5103

AN:

39652

Gnomad4 SAS exome

AF:

0.284

AC:

24477

AN:

86204

Gnomad4 FIN exome

AF:

0.495

AC:

26326

AN:

53166

Gnomad4 NFE exome

AF:

0.437

AC:

485490

AN:

1110600

Gnomad4 Remaining exome

AF:

0.403

AC:

24314

AN:

60296

Heterozygous variant carriers

18545

37090

55635

74180

92725

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

14396

28792

43188

57584

71980

<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:

0.445

AC:

67594

AN:

151892

Hom.:

15919

Cov.:

AF XY:

0.439

AC XY:

32537

AN XY:

74200

show subpopulations

Gnomad4 AFR

AF:

0.558

AC:

0.557604

AN:

0.557604

Gnomad4 AMR

AF:

0.311

AC:

0.311354

AN:

0.311354

Gnomad4 ASJ

AF:

0.371

AC:

0.371396

AN:

0.371396

Gnomad4 EAS

AF:

0.118

AC:

0.117693

AN:

0.117693

Gnomad4 SAS

AF:

0.265

AC:

0.265255

AN:

0.265255

Gnomad4 FIN

AF:

0.504

AC:

0.503786

AN:

0.503786

Gnomad4 NFE

AF:

0.441

AC:

0.440517

AN:

0.440517

Gnomad4 OTH

AF:

0.417

AC:

0.416667

AN:

0.416667

Heterozygous variant carriers

1860

3721

5581

7442

9302

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

604

1208

1812

2416

3020

<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:

0.340

Hom.:

1417

Bravo

AF:

0.435

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.015

DANN

Benign

0.41

Mutation Taster

=100/0

polymorphism (auto)

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