chr1-7786467-A-C

Position:

• chr1-7786467-A-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PER3	NM_001377275.1	c.275-254A>C		intron_variant		ENST00000377532.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PER3	ENST00000377532.8	c.275-254A>C		intron_variant		1	NM_001377275.1	A2

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

Gnomad4 AFR AF: 0.589

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.433

Gnomad4 SAS AF: 0.373

Gnomad4 FIN AF: 0.368

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.375

Alfa AF: 0.384 Hom.: 1630

Bravo AF: 0.413

Asia WGS AF: 0.404 AC: 1403 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.013
DANN	Benign	0.62

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: rs836755; hg19: chr1-7846527;