1-7819567-C-T

Position:

• chr1-7819567-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001377275.1(PER3):​c.1658+147C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 687,684 control chromosomes in the GnomAD database, including 7,156 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 0.14 (1826 hom., cov: 33)
  • Exomes 𝑓: 0.13 (5330 hom.)
• Consequence: PER3 NM_001377275.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14

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]

ENSG00000236266 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PER3	NM_001377275.1	c.1658+147C>T		intron_variant		ENST00000377532.8	NP_001364204.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PER3	ENST00000377532.8	c.1658+147C>T		intron_variant		1	NM_001377275.1	ENSP00000366755.3

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22037 AN: 152010 Hom.: 1823 Cov.: 33

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.0538

Gnomad AMR AF: 0.0954

Gnomad ASJ AF: 0.0452

Gnomad EAS AF: 0.0542

Gnomad SAS AF: 0.0462

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.115

GnomAD4 exome AF: 0.128 AC: 68521 AN: 535556 Hom.: 5330 AF XY: 0.123 AC XY: 35036 AN XY: 285146

Gnomad4 AFR exome AF: 0.154

Gnomad4 AMR exome AF: 0.0762

Gnomad4 ASJ exome AF: 0.0481

Gnomad4 EAS exome AF: 0.0370

Gnomad4 SAS exome AF: 0.0429

Gnomad4 FIN exome AF: 0.239

Gnomad4 NFE exome AF: 0.146

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.145 AC: 22056 AN: 152128 Hom.: 1826 Cov.: 33 AF XY: 0.145 AC XY: 10748 AN XY: 74348

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.0953

Gnomad4 ASJ AF: 0.0452

Gnomad4 EAS AF: 0.0544

Gnomad4 SAS AF: 0.0458

Gnomad4 FIN AF: 0.244

Gnomad4 NFE AF: 0.152

Gnomad4 OTH AF: 0.114

Alfa AF: 0.135 Hom.: 3040

Bravo AF: 0.135

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.0
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10462018; hg19: chr1-7879627;