rs228671

Variant names:

• chr1-7810358-C-T
• rs228671
• NM_001377275.1:c.1372-80C>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.1372-80C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0908 in 1,010,968 control chromosomes in the GnomAD database, including 4,587 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 0.074 (527 hom., cov: 32)
  • Exomes 𝑓: 0.094 (4060 hom.)
• Consequence: PER3 NM_001377275.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.478
• Publications: 9 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377275.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PER3	NM_001377275.1	MANE Select	c.1372-80C>T		intron	N/A	NP_001364204.1	P56645-2
	PER3	NM_001289862.2		c.1372-80C>T		intron	N/A	NP_001276791.1	P56645-2
	PER3	NM_001438696.1		c.1369-80C>T		intron	N/A	NP_001425625.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PER3	ENST00000377532.8	TSL:1 MANE Select	c.1372-80C>T		intron	N/A	ENSP00000366755.3	P56645-2
	PER3	ENST00000361923.2	TSL:1	c.1369-80C>T		intron	N/A	ENSP00000355031.2	P56645-1
	PER3	ENST00000614998.4	TSL:1	c.1372-80C>T		intron	N/A	ENSP00000479223.1	A0A087WV69

Frequencies

GnomAD3 genomes AF: 0.0745 AC: 11335 AN: 152130 Hom.: 526 Cov.: 32

Gnomad AFR AF: 0.0257

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.0693

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.0466

Gnomad SAS AF: 0.0894

Gnomad FIN AF: 0.0740

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0842

GnomAD4 exome AF: 0.0936 AC: 80415 AN: 858720 Hom.: 4060 Cov.: 11 AF XY: 0.0948 AC XY: 41720 AN XY: 440230

African (AFR) AF: 0.0238 AC: 491 AN: 20652

American (AMR) AF: 0.0625 AC: 1705 AN: 27280

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 2636 AN: 17098

East Asian (EAS) AF: 0.0621 AC: 2244 AN: 36116

South Asian (SAS) AF: 0.0953 AC: 5498 AN: 57694

European-Finnish (FIN) AF: 0.0767 AC: 3725 AN: 48560

Middle Eastern (MID) AF: 0.132 AC: 529 AN: 4018

European-Non Finnish (NFE) AF: 0.0987 AC: 59982 AN: 607766

Other (OTH) AF: 0.0912 AC: 3605 AN: 39536

GnomAD4 genome AF: 0.0745 AC: 11335 AN: 152248 Hom.: 527 Cov.: 32 AF XY: 0.0732 AC XY: 5451 AN XY: 74438

African (AFR) AF: 0.0256 AC: 1065 AN: 41552

American (AMR) AF: 0.0692 AC: 1059 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 492 AN: 3468

East Asian (EAS) AF: 0.0465 AC: 241 AN: 5186

South Asian (SAS) AF: 0.0893 AC: 431 AN: 4826

European-Finnish (FIN) AF: 0.0740 AC: 783 AN: 10588

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6944 AN: 68014

Other (OTH) AF: 0.0833 AC: 176 AN: 2112

Alfa AF: 0.0806 Hom.: 72

Bravo AF: 0.0731

Asia WGS AF: 0.0640 AC: 221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.5
DANN	Benign	0.33
PhyloP100		-0.48
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs228671; hg19: chr1-7870418;