1-7824520-T-C

Variant names:

• chr1-7824520-T-C
• rs697690
• NM_001377275.1:c.1958-1960T>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.1958-1960T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 151,878 control chromosomes in the GnomAD database, including 11,854 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 0.38 (11854 hom., cov: 30)
• Consequence: PER3 NM_001377275.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.391
• Publications: 7 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.514 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.1958-1960T>C		intron	N/A	NP_001364204.1
	PER3	NM_001289862.2		c.1958-1960T>C		intron	N/A	NP_001276791.1
	PER3	NM_001438696.1		c.1955-1960T>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.1958-1960T>C		intron	N/A	ENSP00000366755.3
	PER3	ENST00000361923.2	TSL:1	c.1934-1960T>C		intron	N/A	ENSP00000355031.2
	PER3	ENST00000614998.4	TSL:1	c.1958-1960T>C		intron	N/A	ENSP00000479223.1

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57845 AN: 151760 Hom.: 11851 Cov.: 30

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.516

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.347

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

GnomAD4 genome AF: 0.381 AC: 57892 AN: 151878 Hom.: 11854 Cov.: 30 AF XY: 0.376 AC XY: 27932 AN XY: 74264

African (AFR) AF: 0.520 AC: 21532 AN: 41386

American (AMR) AF: 0.262 AC: 3996 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 987 AN: 3468

East Asian (EAS) AF: 0.516 AC: 2666 AN: 5162

South Asian (SAS) AF: 0.339 AC: 1629 AN: 4800

European-Finnish (FIN) AF: 0.323 AC: 3408 AN: 10544

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.334 AC: 22671 AN: 67926

Other (OTH) AF: 0.344 AC: 727 AN: 2114

Alfa AF: 0.358 Hom.: 2592

Bravo AF: 0.382

Asia WGS AF: 0.411 AC: 1428 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.5
DANN	Benign	0.61
PhyloP100		-0.39
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: rs697690; hg19: chr1-7884580;