rs2172563

Variant names:

• chr1-7813983-G-A
• rs2172563
• NM_001377275.1:c.1522+3395G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-7813983-G-A
• chr1-7813983-G-T

Variant summary

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

The NM_001377275.1(PER3):​c.1522+3395G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,184 control chromosomes in the GnomAD database, including 3,199 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 0.20 (3199 hom., cov: 32)
• Consequence: PER3 NM_001377275.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.730
• Publications: 5 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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PER3	NM_001377275.1	c.1522+3395G>A		intron_variant	Intron 13 of 21	ENST00000377532.8	NP_001364204.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PER3	ENST00000377532.8	c.1522+3395G>A		intron_variant	Intron 13 of 21	1	NM_001377275.1	ENSP00000366755.3

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30202 AN: 152064 Hom.: 3188 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.199 AC: 30232 AN: 152184 Hom.: 3199 Cov.: 32 AF XY: 0.202 AC XY: 15010 AN XY: 74408

African (AFR) AF: 0.152 AC: 6312 AN: 41520

American (AMR) AF: 0.163 AC: 2484 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 983 AN: 3470

East Asian (EAS) AF: 0.140 AC: 728 AN: 5182

South Asian (SAS) AF: 0.274 AC: 1322 AN: 4830

European-Finnish (FIN) AF: 0.265 AC: 2800 AN: 10582

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14877 AN: 67998

Other (OTH) AF: 0.220 AC: 466 AN: 2114

Alfa AF: 0.124 Hom.: 223

Bravo AF: 0.187

Asia WGS AF: 0.218 AC: 760 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.21
DANN	Benign	0.52
PhyloP100		-0.73
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: rs2172563; hg19: chr1-7874043; COSMIC: COSV62705033; COSMIC: COSV62705033;