1-7808665-T-C

Variant names:

• chr1-7808665-T-C
• rs228666
• NM_001377275.1:c.1137-228T>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.1137-228T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 152,092 control chromosomes in the GnomAD database, including 7,566 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 0.30 (7566 hom., cov: 32)
• Consequence: PER3 NM_001377275.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.499
• Publications: 19 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PER3	NM_001377275.1	c.1137-228T>C		intron_variant	Intron 10 of 21	ENST00000377532.8	NP_001364204.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PER3	ENST00000377532.8	c.1137-228T>C		intron_variant	Intron 10 of 21	1	NM_001377275.1	ENSP00000366755.3

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46138 AN: 151974 Hom.: 7555 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.304 AC: 46185 AN: 152092 Hom.: 7566 Cov.: 32 AF XY: 0.308 AC XY: 22879 AN XY: 74332

African (AFR) AF: 0.207 AC: 8595 AN: 41534

American (AMR) AF: 0.457 AC: 6985 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 1144 AN: 3466

East Asian (EAS) AF: 0.334 AC: 1725 AN: 5162

South Asian (SAS) AF: 0.305 AC: 1470 AN: 4814

European-Finnish (FIN) AF: 0.324 AC: 3422 AN: 10564

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.322 AC: 21856 AN: 67958

Other (OTH) AF: 0.309 AC: 652 AN: 2108

Alfa AF: 0.320 Hom.: 30909

Bravo AF: 0.313

Asia WGS AF: 0.308 AC: 1068 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.3
DANN	Benign	0.67
PhyloP100		-0.50
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: rs228666; hg19: chr1-7868725;