1-7810358-C-T

Position:

• chr1-7810358-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.1372-80C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0908 in 1,010,968 control chromosomes in the GnomAD database, including 4,587 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 0.074 (527 hom., cov: 32)
  • Exomes 𝑓: 0.094 (4060 hom.)
• Consequence: PER3 NM_001377275.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.478

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PER3	NM_001377275.1	c.1372-80C>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.1372-80C>T		intron_variant		1	NM_001377275.1	ENSP00000366755.3

Frequencies

GnomAD3 genomes AF: 0.0745 AC: 11335 AN: 152130 Hom.: 526 Cov.: 32

Gnomad AFR AF: 0.0257

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.0693

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.0466

Gnomad SAS AF: 0.0894

Gnomad FIN AF: 0.0740

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0842

GnomAD4 exome AF: 0.0936 AC: 80415 AN: 858720 Hom.: 4060 Cov.: 11 AF XY: 0.0948 AC XY: 41720 AN XY: 440230

Gnomad4 AFR exome AF: 0.0238

Gnomad4 AMR exome AF: 0.0625

Gnomad4 ASJ exome AF: 0.154

Gnomad4 EAS exome AF: 0.0621

Gnomad4 SAS exome AF: 0.0953

Gnomad4 FIN exome AF: 0.0767

Gnomad4 NFE exome AF: 0.0987

Gnomad4 OTH exome AF: 0.0912

GnomAD4 genome AF: 0.0745 AC: 11335 AN: 152248 Hom.: 527 Cov.: 32 AF XY: 0.0732 AC XY: 5451 AN XY: 74438

Gnomad4 AFR AF: 0.0256

Gnomad4 AMR AF: 0.0692

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.0465

Gnomad4 SAS AF: 0.0893

Gnomad4 FIN AF: 0.0740

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.0833

Alfa AF: 0.0826 Hom.: 72

Bravo AF: 0.0731

Asia WGS AF: 0.0640 AC: 221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.5
DANN	Benign	0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs228671; hg19: chr1-7870418;