1-7798075-G-C

Variant names:

• chr1-7798075-G-C
• rs1012477
• NM_001377275.1:c.645-450G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001377275.1(PER3):​c.645-450G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,154 control chromosomes in the GnomAD database, including 2,124 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 0.15 (2124 hom., cov: 33)
• Consequence: PER3 NM_001377275.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.527
• Publications: 30 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.196 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PER3	NM_001377275.1	MANE Select	c.645-450G>C		intron	N/A	NP_001364204.1
	PER3	NM_001289862.2		c.645-450G>C		intron	N/A	NP_001276791.1
	PER3	NM_001438696.1		c.642-450G>C		intron	N/A	NP_001425625.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PER3	ENST00000377532.8	TSL:1 MANE Select	c.645-450G>C		intron	N/A	ENSP00000366755.3
	PER3	ENST00000361923.2	TSL:1	c.642-450G>C		intron	N/A	ENSP00000355031.2
	PER3	ENST00000614998.4	TSL:1	c.645-450G>C		intron	N/A	ENSP00000479223.1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23528 AN: 152036 Hom.: 2121 Cov.: 33

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.0946

Gnomad ASJ AF: 0.0452

Gnomad EAS AF: 0.0408

Gnomad SAS AF: 0.0432

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.155 AC: 23549 AN: 152154 Hom.: 2124 Cov.: 33 AF XY: 0.154 AC XY: 11491 AN XY: 74378

African (AFR) AF: 0.199 AC: 8273 AN: 41480

American (AMR) AF: 0.0944 AC: 1443 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0452 AC: 157 AN: 3470

East Asian (EAS) AF: 0.0411 AC: 213 AN: 5186

South Asian (SAS) AF: 0.0429 AC: 207 AN: 4830

European-Finnish (FIN) AF: 0.242 AC: 2563 AN: 10580

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.153 AC: 10381 AN: 68014

Other (OTH) AF: 0.120 AC: 253 AN: 2110

Alfa AF: 0.162 Hom.: 301

Bravo AF: 0.146

Asia WGS AF: 0.0660 AC: 232 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.0
DANN	Benign	0.80
PhyloP100		0.53
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: rs1012477; hg19: chr1-7858135;