chr1-7821720-C-T

Variant names:

• chr1-7821720-C-T
• rs10127838
• NM_001377275.1:c.1957+1080C>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.1957+1080C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,084 control chromosomes in the GnomAD database, including 3,177 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 (3177 hom., cov: 32)
• Consequence: PER3 NM_001377275.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.335
• Publications: 12 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.26 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.1957+1080C>T		intron	N/A	NP_001364204.1	P56645-2
	PER3	NM_001289862.2		c.1957+1080C>T		intron	N/A	NP_001276791.1	P56645-2
	PER3	NM_001438696.1		c.1954+1080C>T		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.1957+1080C>T		intron	N/A	ENSP00000366755.3	P56645-2
	PER3	ENST00000361923.2	TSL:1	c.1933+1080C>T		intron	N/A	ENSP00000355031.2	P56645-1
	PER3	ENST00000614998.4	TSL:1	c.1957+1080C>T		intron	N/A	ENSP00000479223.1	A0A087WV69

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30132 AN: 151966 Hom.: 3166 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.264

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: 0.198 AC: 30161 AN: 152084 Hom.: 3177 Cov.: 32 AF XY: 0.201 AC XY: 14964 AN XY: 74326

African (AFR) AF: 0.152 AC: 6309 AN: 41490

American (AMR) AF: 0.161 AC: 2462 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 979 AN: 3464

East Asian (EAS) AF: 0.141 AC: 729 AN: 5182

South Asian (SAS) AF: 0.272 AC: 1312 AN: 4820

European-Finnish (FIN) AF: 0.264 AC: 2789 AN: 10546

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

European-Non Finnish (NFE) AF: 0.219 AC: 14856 AN: 67962

Other (OTH) AF: 0.220 AC: 465 AN: 2110

Alfa AF: 0.212 Hom.: 14862

Bravo AF: 0.187

Asia WGS AF: 0.220 AC: 768 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.55
DANN	Benign	0.66
PhyloP100		-0.34
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: rs10127838; hg19: chr1-7881780; COSMIC: COSV62705045;