1-7796286-T-C

Variant names:

• chr1-7796286-T-C
• rs228682
• NM_001377275.1:c.645-2239T>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.645-2239T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 149,090 control chromosomes in the GnomAD database, including 9,838 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 0.35 (9838 hom., cov: 27)
• Consequence: PER3 NM_001377275.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0110
• Publications: 28 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PER3	NM_001377275.1	c.645-2239T>C		intron_variant	Intron 6 of 21	ENST00000377532.8	NP_001364204.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PER3	ENST00000377532.8	c.645-2239T>C		intron_variant	Intron 6 of 21	1	NM_001377275.1	ENSP00000366755.3

Frequencies

GnomAD3 genomes AF: 0.351 AC: 52322 AN: 148996 Hom.: 9834 Cov.: 27

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.613

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.351 AC: 52339 AN: 149090 Hom.: 9838 Cov.: 27 AF XY: 0.351 AC XY: 25391 AN XY: 72414

African (AFR) AF: 0.262 AC: 10597 AN: 40522

American (AMR) AF: 0.313 AC: 4634 AN: 14818

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 1733 AN: 3438

East Asian (EAS) AF: 0.198 AC: 1003 AN: 5062

South Asian (SAS) AF: 0.424 AC: 2015 AN: 4752

European-Finnish (FIN) AF: 0.380 AC: 3660 AN: 9636

Middle Eastern (MID) AF: 0.614 AC: 178 AN: 290

European-Non Finnish (NFE) AF: 0.403 AC: 27250 AN: 67598

Other (OTH) AF: 0.396 AC: 820 AN: 2072

Alfa AF: 0.403 Hom.: 19045

Bravo AF: 0.343

Asia WGS AF: 0.332 AC: 1155 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.3
DANN	Benign	0.66
PhyloP100		-0.011
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: rs228682; hg19: chr1-7856346; COSMIC: COSV62704992;