1-7794938-G-T

Position:

• chr1-7794938-G-T

Variant summary

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

The NM_001377275.1(PER3):​c.644+930G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 151,434 control chromosomes in the GnomAD database, including 12,017 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 0.38 (12017 hom., cov: 32)
• Consequence: PER3 NM_001377275.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.331

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PER3	NM_001377275.1	c.644+930G>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.644+930G>T		intron_variant		1	NM_001377275.1	ENSP00000366755	A2

Frequencies

GnomAD3 genomes AF: 0.383 AC: 57967 AN: 151350 Hom.: 12007 Cov.: 32

Gnomad AFR AF: 0.543

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.348

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.383 AC: 58012 AN: 151434 Hom.: 12017 Cov.: 32 AF XY: 0.377 AC XY: 27881 AN XY: 73958

Gnomad4 AFR AF: 0.543

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.283

Gnomad4 EAS AF: 0.431

Gnomad4 SAS AF: 0.336

Gnomad4 FIN AF: 0.302

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.345

Alfa AF: 0.291 Hom.: 1589

Bravo AF: 0.386

Asia WGS AF: 0.387 AC: 1345 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.43
DANN	Benign	0.30

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: rs696306; hg19: chr1-7854998;