1-7828155-A-G

Variant names:

• chr1-7828155-A-G
• rs2859388
• NM_001377275.1:c.2886+340A>G

Variant summary

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

The NM_001377275.1(PER3):​c.2886+340A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 152,044 control chromosomes in the GnomAD database, including 15,554 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 0.44 (15554 hom., cov: 33)
• Consequence: PER3 NM_001377275.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.665
• Publications: 8 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PER3	NM_001377275.1	c.2886+340A>G		intron_variant	Intron 18 of 21	ENST00000377532.8	NP_001364204.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PER3	ENST00000377532.8	c.2886+340A>G		intron_variant	Intron 18 of 21	1	NM_001377275.1	ENSP00000366755.3
PER3	ENST00000361923.2	c.2862+340A>G		intron_variant	Intron 17 of 20	1		ENSP00000355031.2
PER3	ENST00000614998.4	c.2886+340A>G		intron_variant	Intron 18 of 22	1		ENSP00000479223.1
PER3	ENST00000613533.4	c.2886+340A>G		intron_variant	Intron 18 of 21	5		ENSP00000482093.1

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66207 AN: 151926 Hom.: 15542 Cov.: 33

Gnomad AFR AF: 0.552

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.789

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.274

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.405

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

GnomAD4 genome AF: 0.436 AC: 66267 AN: 152044 Hom.: 15554 Cov.: 33 AF XY: 0.435 AC XY: 32296 AN XY: 74306

African (AFR) AF: 0.552 AC: 22890 AN: 41464

American (AMR) AF: 0.454 AC: 6932 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1094 AN: 3466

East Asian (EAS) AF: 0.789 AC: 4086 AN: 5180

South Asian (SAS) AF: 0.382 AC: 1840 AN: 4814

European-Finnish (FIN) AF: 0.334 AC: 3525 AN: 10562

Middle Eastern (MID) AF: 0.274 AC: 80 AN: 292

European-Non Finnish (NFE) AF: 0.364 AC: 24715 AN: 67960

Other (OTH) AF: 0.403 AC: 852 AN: 2116

Alfa AF: 0.402 Hom.: 19844

Bravo AF: 0.454

Asia WGS AF: 0.578 AC: 2009 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.63
DANN	Benign	0.40
PhyloP100		-0.67
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: rs2859388; hg19: chr1-7888215;