1-7819003-C-T

Variant names:

• chr1-7819003-C-T
• rs2797685
• NM_001377275.1:c.1523-282C>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.1523-282C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 152,162 control chromosomes in the GnomAD database, including 4,869 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 0.23 (4869 hom., cov: 33)
• Consequence: PER3 NM_001377275.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0670
• Publications: 48 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PER3	NM_001377275.1	c.1523-282C>T		intron_variant	Intron 13 of 21	ENST00000377532.8	NP_001364204.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PER3	ENST00000377532.8	c.1523-282C>T		intron_variant	Intron 13 of 21	1	NM_001377275.1	ENSP00000366755.3

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35380 AN: 152044 Hom.: 4870 Cov.: 33

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.0815

Gnomad MID AF: 0.208

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.233 AC: 35406 AN: 152162 Hom.: 4869 Cov.: 33 AF XY: 0.228 AC XY: 16983 AN XY: 74404

African (AFR) AF: 0.344 AC: 14265 AN: 41504

American (AMR) AF: 0.168 AC: 2568 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 828 AN: 3472

East Asian (EAS) AF: 0.475 AC: 2450 AN: 5156

South Asian (SAS) AF: 0.297 AC: 1433 AN: 4822

European-Finnish (FIN) AF: 0.0815 AC: 865 AN: 10616

Middle Eastern (MID) AF: 0.207 AC: 60 AN: 290

European-Non Finnish (NFE) AF: 0.181 AC: 12305 AN: 67988

Other (OTH) AF: 0.226 AC: 477 AN: 2106

Alfa AF: 0.207 Hom.: 11406

Bravo AF: 0.243

Asia WGS AF: 0.346 AC: 1200 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	4.2
DANN	Benign	0.56
PhyloP100		-0.067
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: rs2797685; hg19: chr1-7879063;