rs228642

chr1-7803233-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001377275.1(PER3):c.979+80C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 855,818 control chromosomes in the GnomAD database, including 125,711 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 0.50 (19808 hom., cov: 31)
  • Exomes 𝑓: 0.54 (105903 hom.)
• Consequence: PER3 NM_001377275.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.814

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PER3	NM_001377275.1	c.979+80C>T		intron_variant		ENST00000377532.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PER3	ENST00000377532.8	c.979+80C>T		intron_variant		1	NM_001377275.1	A2

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75128 AN: 151528 Hom.: 19801 Cov.: 31

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.527

GnomAD4 exome AF: 0.539 AC: 379784 AN: 704174 Hom.: 105903 AF XY: 0.546 AC XY: 206077 AN XY: 377264

Gnomad4 AFR exome AF: 0.359

Gnomad4 AMR exome AF: 0.412

Gnomad4 ASJ exome AF: 0.632

Gnomad4 EAS exome AF: 0.245

Gnomad4 SAS exome AF: 0.573

Gnomad4 FIN exome AF: 0.555

Gnomad4 NFE exome AF: 0.572

Gnomad4 OTH exome AF: 0.534

GnomAD4 genome AF: 0.496 AC: 75174 AN: 151644 Hom.: 19808 Cov.: 31 AF XY: 0.496 AC XY: 36769 AN XY: 74116

Gnomad4 AFR AF: 0.358

Gnomad4 AMR AF: 0.498

Gnomad4 ASJ AF: 0.643

Gnomad4 EAS AF: 0.211

Gnomad4 SAS AF: 0.564

Gnomad4 FIN AF: 0.571

Gnomad4 NFE AF: 0.573

Gnomad4 OTH AF: 0.530

Alfa AF: 0.559 Hom.: 46420

Bravo AF: 0.480

Asia WGS AF: 0.386 AC: 1342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.36
Dann	Benign	0.57

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

Other links and lift over

dbSNP: rs228642; hg19: chr1-7863293; COSMIC: COSV62707785;