1-7787776-T-C

Variant names:

• chr1-7787776-T-C
• rs228727
• NM_001377275.1:c.391-269T>C

Variant summary

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

The NM_001377275.1(PER3):​c.391-269T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.604 in 452,418 control chromosomes in the GnomAD database, including 84,717 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 0.56 (25571 hom., cov: 33)
  • Exomes 𝑓: 0.62 (59146 hom.)
• Consequence: PER3 NM_001377275.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.502

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PER3	NM_001377275.1	c.391-269T>C		intron_variant	Intron 4 of 21	ENST00000377532.8	NP_001364204.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PER3	ENST00000377532.8	c.391-269T>C		intron_variant	Intron 4 of 21	1	NM_001377275.1	ENSP00000366755.3

Frequencies

GnomAD3 genomes AF: 0.565 AC: 85885 AN: 152056 Hom.: 25560 Cov.: 33

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.698

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.644

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.623

Gnomad OTH AF: 0.604

GnomAD4 exome AF: 0.623 AC: 187198 AN: 300244 Hom.: 59146 Cov.: 2 AF XY: 0.628 AC XY: 100470 AN XY: 159902

Gnomad4 AFR exome AF: 0.365

Gnomad4 AMR exome AF: 0.723

Gnomad4 ASJ exome AF: 0.682

Gnomad4 EAS exome AF: 0.565

Gnomad4 SAS exome AF: 0.653

Gnomad4 FIN exome AF: 0.646

Gnomad4 NFE exome AF: 0.623

Gnomad4 OTH exome AF: 0.619

GnomAD4 genome AF: 0.565 AC: 85926 AN: 152174 Hom.: 25571 Cov.: 33 AF XY: 0.572 AC XY: 42516 AN XY: 74372

Gnomad4 AFR AF: 0.370

Gnomad4 AMR AF: 0.698

Gnomad4 ASJ AF: 0.691

Gnomad4 EAS AF: 0.567

Gnomad4 SAS AF: 0.644

Gnomad4 FIN AF: 0.663

Gnomad4 NFE AF: 0.623

Gnomad4 OTH AF: 0.607

Alfa AF: 0.524 Hom.: 2407

Bravo AF: 0.559

Asia WGS AF: 0.593 AC: 2062 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.36
DANN	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs228727; hg19: chr1-7847836;