dbSNP rs228730: PER3:c.-225+33G>A (chr1-7784409-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001377275.1(PER3):c.-225+33G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0729 in 150,850 control chromosomes in the GnomAD database, including 511 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 0.073 ( 509 hom., cov: 32)

Exomes 𝑓: 0.069 ( 2 hom. )

Consequence

PER3
NM_001377275.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.368

Publications

6 publications found

Variant links:

Genes affected

PER3 (HGNC:8847): (period circadian regulator 3) 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 have been linked to sleep disorders. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2014]

PER3 Gene-Disease associations (from GenCC):

advanced sleep phase syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

PER3 links:

Genome browser will be placed here

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=-0.8).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0999 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PER3	NM_001377275.1 link	c.-225+33G>A		intron_variant	Intron 1 of 21	ENST00000377532.8	NP_001364204.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PER3	ENST00000377532.8 link	c.-225+33G>A	intron_variant	Intron 1 of 21	1	NM_001377275.1	ENSP00000366755.3	P56645-2
PER3	ENST00000377541.5 link	c.-225+33G>A	intron_variant	Intron 1 of 9	1		ENSP00000366764.1	Q8TAR6
PER3	ENST00000614998.4 link	c.-284G>A	upstream_gene_variant		1		ENSP00000479223.1	A0A087WV69
PER3	ENST00000613533.4 link	c.-284G>A	upstream_gene_variant		5		ENSP00000482093.1	P56645-2

Frequencies

GnomAD3 genomes

AF:

0.0730

AC:

10967

AN:

150220

Hom.:

508

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0219

Gnomad AMI

AF:

0.120

Gnomad AMR

AF:

0.0687

Gnomad ASJ

AF:

0.140

Gnomad EAS

AF:

0.0464

Gnomad SAS

AF:

0.0922

Gnomad FIN

AF:

0.0698

Gnomad MID

AF:

0.126

Gnomad NFE

AF:

0.102

Gnomad OTH

AF:

0.0837

GnomAD4 exome

AF:

0.0692

AC:

AN:

520

Hom.:

Cov.:

AF XY:

0.0582

AC XY:

AN XY:

378

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.0625

AC:

AN:

South Asian (SAS)

AF:

0.0750

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0704

AC:

AN:

398

Other (OTH)

AF:

0.150

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0729

AC:

10966

AN:

150330

Hom.:

509

Cov.:

AF XY:

0.0716

AC XY:

5262

AN XY:

73458

show subpopulations

African (AFR)

AF:

0.0219

AC:

904

AN:

41320

American (AMR)

AF:

0.0686

AC:

1035

AN:

15080

Ashkenazi Jewish (ASJ)

AF:

0.140

AC:

482

AN:

3454

East Asian (EAS)

AF:

0.0464

AC:

237

AN:

5108

South Asian (SAS)

AF:

0.0920

AC:

437

AN:

4748

European-Finnish (FIN)

AF:

0.0698

AC:

712

AN:

10200

Middle Eastern (MID)

AF:

0.132

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.102

AC:

6844

AN:

67182

Other (OTH)

AF:

0.0827

AC:

171

AN:

2068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

523

1046

1569

2092

2615

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

130

260

390

520

650

<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:

0.0317

Hom.:

Bravo

AF:

0.0710

Asia WGS

AF:

0.0610

AC:

210

AN:

3436

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.2

(source)

DANN

Benign

0.85

PhyloP100

-0.37

PromoterAI

-0.024

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over