rs697686

Variant names:

• chr1-7790158-C-T
• rs697686
• NM_001377275.1:c.592+1912C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001377275.1(PER3):​c.592+1912C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 151,950 control chromosomes in the GnomAD database, including 12,983 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 0.40 (12983 hom., cov: 33)
• Consequence: PER3 NM_001377275.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.238
• Publications: 15 publications found

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

ENSG00000236266 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PER3	NM_001377275.1	c.592+1912C>T		intron_variant	Intron 5 of 21	ENST00000377532.8	NP_001364204.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PER3	ENST00000377532.8	c.592+1912C>T		intron_variant	Intron 5 of 21	1	NM_001377275.1	ENSP00000366755.3

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60755 AN: 151832 Hom.: 12969 Cov.: 33

Gnomad AFR AF: 0.547

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.364

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.400 AC: 60819 AN: 151950 Hom.: 12983 Cov.: 33 AF XY: 0.396 AC XY: 29423 AN XY: 74278

African (AFR) AF: 0.547 AC: 22657 AN: 41396

American (AMR) AF: 0.277 AC: 4230 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1040 AN: 3470

East Asian (EAS) AF: 0.430 AC: 2216 AN: 5154

South Asian (SAS) AF: 0.368 AC: 1776 AN: 4826

European-Finnish (FIN) AF: 0.370 AC: 3901 AN: 10546

Middle Eastern (MID) AF: 0.248 AC: 72 AN: 290

European-Non Finnish (NFE) AF: 0.352 AC: 23959 AN: 67970

Other (OTH) AF: 0.361 AC: 762 AN: 2108

Alfa AF: 0.365 Hom.: 28093

Bravo AF: 0.398

Asia WGS AF: 0.400 AC: 1391 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.3
DANN	Benign	0.61
PhyloP100		0.24
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

Other links and lift over

dbSNP: rs697686; hg19: chr1-7850218;