rs228644

Variant names:

• chr1-7806023-G-A
• rs228644
• NM_001377275.1:c.1136+2175G>A

Variant summary

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

The NM_001377275.1(PER3):​c.1136+2175G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 152,006 control chromosomes in the GnomAD database, including 10,164 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 0.36 (10164 hom., cov: 32)
• Consequence: PER3 NM_001377275.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.438
• Publications: 13 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PER3	NM_001377275.1	c.1136+2175G>A		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.1136+2175G>A		intron_variant	Intron 10 of 21	1	NM_001377275.1	ENSP00000366755.3

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54071 AN: 151888 Hom.: 10162 Cov.: 32

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.601

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: 0.356 AC: 54088 AN: 152006 Hom.: 10164 Cov.: 32 AF XY: 0.356 AC XY: 26436 AN XY: 74270

African (AFR) AF: 0.274 AC: 11369 AN: 41454

American (AMR) AF: 0.321 AC: 4901 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1746 AN: 3470

East Asian (EAS) AF: 0.199 AC: 1034 AN: 5184

South Asian (SAS) AF: 0.422 AC: 2028 AN: 4810

European-Finnish (FIN) AF: 0.394 AC: 4145 AN: 10524

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.403 AC: 27399 AN: 67966

Other (OTH) AF: 0.396 AC: 837 AN: 2112

Alfa AF: 0.381 Hom.: 2452

Bravo AF: 0.345

Asia WGS AF: 0.328 AC: 1143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
DANN	Benign	0.34
PhyloP100		0.44
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: rs228644; hg19: chr1-7866083; COSMIC: COSV62705018; COSMIC: COSV62705018;