rs2859388

Positions:

• chr1-7828155-A-G

Variant summary

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

The NM_001377275.1(PER3):​c.2886+340A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 152,044 control chromosomes in the GnomAD database, including 15,554 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 0.44 (15554 hom., cov: 33)
• Consequence: PER3 NM_001377275.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.665

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PER3	NM_001377275.1	c.2886+340A>G		intron_variant		ENST00000377532.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PER3	ENST00000377532.8	c.2886+340A>G		intron_variant		1	NM_001377275.1	A2
PER3	ENST00000361923.2	c.2862+340A>G		intron_variant		1		P2
PER3	ENST00000614998.4	c.2886+340A>G		intron_variant		1		A2
PER3	ENST00000613533.4	c.2886+340A>G		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66207 AN: 151926 Hom.: 15542 Cov.: 33

Gnomad AFR AF: 0.552

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.789

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.274

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.405

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

GnomAD4 genome AF: 0.436 AC: 66267 AN: 152044 Hom.: 15554 Cov.: 33 AF XY: 0.435 AC XY: 32296 AN XY: 74306

Gnomad4 AFR AF: 0.552

Gnomad4 AMR AF: 0.454

Gnomad4 ASJ AF: 0.316

Gnomad4 EAS AF: 0.789

Gnomad4 SAS AF: 0.382

Gnomad4 FIN AF: 0.334

Gnomad4 NFE AF: 0.364

Gnomad4 OTH AF: 0.403

Alfa AF: 0.391 Hom.: 2529

Bravo AF: 0.454

Asia WGS AF: 0.578 AC: 2009 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.63
DANN	Benign	0.40

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: rs2859388; hg19: chr1-7888215;