1-7794938-G-T

Variant names:

• chr1-7794938-G-T
• rs696306
• NM_001377275.1:c.644+930G>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.644+930G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 151,434 control chromosomes in the GnomAD database, including 12,017 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 0.38 (12017 hom., cov: 32)
• Consequence: PER3 NM_001377275.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.331
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.537 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.644+930G>T		intron	N/A	NP_001364204.1
	PER3	NM_001289862.2		c.644+930G>T		intron	N/A	NP_001276791.1
	PER3	NM_001438696.1		c.641+930G>T		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.644+930G>T		intron	N/A	ENSP00000366755.3
	PER3	ENST00000361923.2	TSL:1	c.641+930G>T		intron	N/A	ENSP00000355031.2
	PER3	ENST00000614998.4	TSL:1	c.644+930G>T		intron	N/A	ENSP00000479223.1

Frequencies

GnomAD3 genomes AF: 0.383 AC: 57967 AN: 151350 Hom.: 12007 Cov.: 32

Gnomad AFR AF: 0.543

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.348

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

GnomAD4 genome AF: 0.383 AC: 58012 AN: 151434 Hom.: 12017 Cov.: 32 AF XY: 0.377 AC XY: 27881 AN XY: 73958

African (AFR) AF: 0.543 AC: 22424 AN: 41310

American (AMR) AF: 0.267 AC: 4065 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 982 AN: 3464

East Asian (EAS) AF: 0.431 AC: 2223 AN: 5160

South Asian (SAS) AF: 0.336 AC: 1614 AN: 4800

European-Finnish (FIN) AF: 0.302 AC: 3124 AN: 10332

Middle Eastern (MID) AF: 0.239 AC: 67 AN: 280

European-Non Finnish (NFE) AF: 0.333 AC: 22583 AN: 67850

Other (OTH) AF: 0.345 AC: 726 AN: 2102

Alfa AF: 0.291 Hom.: 1589

Bravo AF: 0.386

Asia WGS AF: 0.387 AC: 1345 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.43
DANN	Benign	0.30
PhyloP100		-0.33
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: rs696306; hg19: chr1-7854998;