1-7819567-C-T

Variant names:

• chr1-7819567-C-T
• rs10462018
• NM_001377275.1:c.1658+147C>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.1658+147C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 687,684 control chromosomes in the GnomAD database, including 7,156 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 0.14 (1826 hom., cov: 33)
  • Exomes 𝑓: 0.13 (5330 hom.)
• Consequence: PER3 NM_001377275.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 25 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.158 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.1658+147C>T		intron	N/A	NP_001364204.1	P56645-2
	PER3	NM_001289862.2		c.1658+147C>T		intron	N/A	NP_001276791.1	P56645-2
	PER3	NM_001438696.1		c.1655+147C>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.1658+147C>T		intron	N/A	ENSP00000366755.3	P56645-2
	PER3	ENST00000361923.2	TSL:1	c.1634+147C>T		intron	N/A	ENSP00000355031.2	P56645-1
	PER3	ENST00000614998.4	TSL:1	c.1658+147C>T		intron	N/A	ENSP00000479223.1	A0A087WV69

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22037 AN: 152010 Hom.: 1823 Cov.: 33

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.0538

Gnomad AMR AF: 0.0954

Gnomad ASJ AF: 0.0452

Gnomad EAS AF: 0.0542

Gnomad SAS AF: 0.0462

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.115

GnomAD4 exome AF: 0.128 AC: 68521 AN: 535556 Hom.: 5330 AF XY: 0.123 AC XY: 35036 AN XY: 285146

African (AFR) AF: 0.154 AC: 2230 AN: 14458

American (AMR) AF: 0.0762 AC: 1892 AN: 24836

Ashkenazi Jewish (ASJ) AF: 0.0481 AC: 698 AN: 14512

East Asian (EAS) AF: 0.0370 AC: 1274 AN: 34438

South Asian (SAS) AF: 0.0429 AC: 2134 AN: 49710

European-Finnish (FIN) AF: 0.239 AC: 8318 AN: 34752

Middle Eastern (MID) AF: 0.0237 AC: 52 AN: 2190

European-Non Finnish (NFE) AF: 0.146 AC: 48297 AN: 331696

Other (OTH) AF: 0.125 AC: 3626 AN: 28964

GnomAD4 genome AF: 0.145 AC: 22056 AN: 152128 Hom.: 1826 Cov.: 33 AF XY: 0.145 AC XY: 10748 AN XY: 74348

African (AFR) AF: 0.162 AC: 6708 AN: 41488

American (AMR) AF: 0.0953 AC: 1456 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0452 AC: 157 AN: 3472

East Asian (EAS) AF: 0.0544 AC: 281 AN: 5170

South Asian (SAS) AF: 0.0458 AC: 221 AN: 4824

European-Finnish (FIN) AF: 0.244 AC: 2575 AN: 10568

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

European-Non Finnish (NFE) AF: 0.152 AC: 10359 AN: 68008

Other (OTH) AF: 0.114 AC: 240 AN: 2110

Alfa AF: 0.140 Hom.: 6698

Bravo AF: 0.135

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.0
DANN	Benign	0.64
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs10462018; hg19: chr1-7879627;