rs228729

chr1-7785635-T-C

Variant summary

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

The NM_001377275.1(PER3):c.274+49T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 1,539,780 control chromosomes in the GnomAD database, including 346,397 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 0.69 (36271 hom., cov: 32)
  • Exomes 𝑓: 0.67 (310126 hom.)
• Consequence: PER3 NM_001377275.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PER3	NM_001377275.1	c.274+49T>C		intron_variant		ENST00000377532.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PER3	ENST00000377532.8	c.274+49T>C		intron_variant		1	NM_001377275.1	A2

Frequencies

GnomAD3 genomes AF: 0.687 AC: 104395 AN: 151988 Hom.: 36227 Cov.: 32

Gnomad AFR AF: 0.748

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.721

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.749

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.656

Gnomad OTH AF: 0.659

GnomAD3 exomes AF: 0.690 AC: 157632 AN: 228582 Hom.: 54837 AF XY: 0.680 AC XY: 84321 AN XY: 124004

Gnomad AFR exome AF: 0.753

Gnomad AMR exome AF: 0.828

Gnomad ASJ exome AF: 0.630

Gnomad EAS exome AF: 0.760

Gnomad SAS exome AF: 0.649

Gnomad FIN exome AF: 0.650

Gnomad NFE exome AF: 0.654

Gnomad OTH exome AF: 0.675

GnomAD4 exome AF: 0.666 AC: 924835 AN: 1387674 Hom.: 310126 Cov.: 20 AF XY: 0.663 AC XY: 456863 AN XY: 688980

Gnomad4 AFR exome AF: 0.751

Gnomad4 AMR exome AF: 0.815

Gnomad4 ASJ exome AF: 0.634

Gnomad4 EAS exome AF: 0.741

Gnomad4 SAS exome AF: 0.643

Gnomad4 FIN exome AF: 0.652

Gnomad4 NFE exome AF: 0.659

Gnomad4 OTH exome AF: 0.665

GnomAD4 genome AF: 0.687 AC: 104492 AN: 152106 Hom.: 36271 Cov.: 32 AF XY: 0.685 AC XY: 50895 AN XY: 74322

Gnomad4 AFR AF: 0.749

Gnomad4 AMR AF: 0.721

Gnomad4 ASJ AF: 0.622

Gnomad4 EAS AF: 0.749

Gnomad4 SAS AF: 0.647

Gnomad4 FIN AF: 0.631

Gnomad4 NFE AF: 0.656

Gnomad4 OTH AF: 0.655

Alfa AF: 0.660 Hom.: 46408

Bravo AF: 0.698

Asia WGS AF: 0.689 AC: 2393 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.24
Dann	Benign	0.74

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: rs228729; hg19: chr1-7845695;