rs836755

Variant names:

• chr1-7786467-A-C
• rs836755
• NM_001377275.1:c.275-254A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-7786467-A-C
• chr1-7786467-A-G
• chr1-7786467-A-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.275-254A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 151,160 control chromosomes in the GnomAD database, including 14,039 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 0.41 (14039 hom., cov: 32)
• Consequence: PER3 NM_001377275.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.32
• Publications: 8 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.582 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PER3	NM_001377275.1	MANE Select	c.275-254A>C		intron	N/A	NP_001364204.1	P56645-2
	PER3	NM_001289862.2		c.275-254A>C		intron	N/A	NP_001276791.1	P56645-2
	PER3	NM_001438696.1		c.275-254A>C		intron	N/A	NP_001425625.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PER3	ENST00000377532.8	TSL:1 MANE Select	c.275-254A>C		intron	N/A	ENSP00000366755.3	P56645-2
	PER3	ENST00000361923.2	TSL:1	c.275-254A>C		intron	N/A	ENSP00000355031.2	P56645-1
	PER3	ENST00000614998.4	TSL:1	c.275-254A>C		intron	N/A	ENSP00000479223.1	A0A087WV69

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62583 AN: 151044 Hom.: 14018 Cov.: 32

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.414 AC: 62652 AN: 151160 Hom.: 14039 Cov.: 32 AF XY: 0.410 AC XY: 30322 AN XY: 73900

African (AFR) AF: 0.589 AC: 24351 AN: 41368

American (AMR) AF: 0.284 AC: 4308 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1046 AN: 3422

East Asian (EAS) AF: 0.433 AC: 2237 AN: 5170

South Asian (SAS) AF: 0.373 AC: 1777 AN: 4766

European-Finnish (FIN) AF: 0.368 AC: 3879 AN: 10536

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.356 AC: 23986 AN: 67424

Other (OTH) AF: 0.375 AC: 787 AN: 2098

Alfa AF: 0.392 Hom.: 1760

Bravo AF: 0.413

Asia WGS AF: 0.404 AC: 1403 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.013
DANN	Benign	0.62
PhyloP100		-2.3
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: rs836755; hg19: chr1-7846527;