NM_001377275.1:c.872+433A>C

Variant names:

• chr1-7801624-A-C
• rs707467
• NM_001377275.1:c.872+433A>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.872+433A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,108 control chromosomes in the GnomAD database, including 4,398 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 0.22 (4398 hom., cov: 32)
• Consequence: PER3 NM_001377275.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.390
• Publications: 20 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377275.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PER3	NM_001377275.1	MANE Select	c.872+433A>C		intron	N/A	NP_001364204.1
	PER3	NM_001289862.2		c.872+433A>C		intron	N/A	NP_001276791.1
	PER3	NM_001438696.1		c.869+433A>C		intron	N/A	NP_001425625.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PER3	ENST00000377532.8	TSL:1 MANE Select	c.872+433A>C		intron	N/A	ENSP00000366755.3
	PER3	ENST00000361923.2	TSL:1	c.869+433A>C		intron	N/A	ENSP00000355031.2
	PER3	ENST00000614998.4	TSL:1	c.872+433A>C		intron	N/A	ENSP00000479223.1

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33893 AN: 151990 Hom.: 4400 Cov.: 32

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.0813

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.223 AC: 33917 AN: 152108 Hom.: 4398 Cov.: 32 AF XY: 0.218 AC XY: 16246 AN XY: 74380

African (AFR) AF: 0.306 AC: 12689 AN: 41434

American (AMR) AF: 0.169 AC: 2585 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 828 AN: 3472

East Asian (EAS) AF: 0.475 AC: 2457 AN: 5172

South Asian (SAS) AF: 0.297 AC: 1436 AN: 4828

European-Finnish (FIN) AF: 0.0813 AC: 862 AN: 10608

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12380 AN: 67992

Other (OTH) AF: 0.219 AC: 464 AN: 2114

Alfa AF: 0.197 Hom.: 5935

Bravo AF: 0.232

Asia WGS AF: 0.347 AC: 1203 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.8
DANN	Benign	0.39
PhyloP100		-0.39
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: rs707467; hg19: chr1-7861684;