1-7803233-C-T

Variant names:

• chr1-7803233-C-T
• rs228642
• NM_001377275.1:c.979+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.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
• Publications: 32 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.568 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.979+80C>T		intron	N/A	NP_001364204.1	P56645-2
	PER3	NM_001289862.2		c.979+80C>T		intron	N/A	NP_001276791.1	P56645-2
	PER3	NM_001438696.1		c.976+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.979+80C>T		intron	N/A	ENSP00000366755.3	P56645-2
	PER3	ENST00000361923.2	TSL:1	c.976+80C>T		intron	N/A	ENSP00000355031.2	P56645-1
	PER3	ENST00000614998.4	TSL:1	c.979+80C>T		intron	N/A	ENSP00000479223.1	A0A087WV69

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

African (AFR) AF: 0.359 AC: 6942 AN: 19334

American (AMR) AF: 0.412 AC: 16947 AN: 41114

Ashkenazi Jewish (ASJ) AF: 0.632 AC: 13369 AN: 21150

East Asian (EAS) AF: 0.245 AC: 8883 AN: 36212

South Asian (SAS) AF: 0.573 AC: 40109 AN: 70018

European-Finnish (FIN) AF: 0.555 AC: 28434 AN: 51246

Middle Eastern (MID) AF: 0.627 AC: 2429 AN: 3872

European-Non Finnish (NFE) AF: 0.572 AC: 243703 AN: 425690

Other (OTH) AF: 0.534 AC: 18968 AN: 35538

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

African (AFR) AF: 0.358 AC: 14785 AN: 41252

American (AMR) AF: 0.498 AC: 7562 AN: 15194

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 2226 AN: 3462

East Asian (EAS) AF: 0.211 AC: 1092 AN: 5168

South Asian (SAS) AF: 0.564 AC: 2713 AN: 4812

European-Finnish (FIN) AF: 0.571 AC: 6027 AN: 10548

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.573 AC: 38900 AN: 67902

Other (OTH) AF: 0.530 AC: 1116 AN: 2104

Alfa AF: 0.546 Hom.: 90647

Bravo AF: 0.480

Asia WGS AF: 0.386 AC: 1342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.36
DANN	Benign	0.57
PhyloP100		-0.81
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: rs228642; hg19: chr1-7863293; COSMIC: COSV62707785;