rs228730

Positions:

• chr1-7784409-G-A
• chr1-7784409-G-T

Variant summary

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

The NM_016831.4(PER3):​c.-284G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0729 in 150,850 control chromosomes in the GnomAD database, including 511 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 0.073 (509 hom., cov: 32)
  • Exomes 𝑓: 0.069 (2 hom.)
• Consequence: PER3 NM_016831.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.368

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0999 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PER3	NM_001377275.1	c.-225+33G>A		intron_variant		ENST00000377532.8	NP_001364204.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PER3	ENST00000377532.8	c.-225+33G>A		intron_variant		1	NM_001377275.1	ENSP00000366755.3
PER3	ENST00000377541.5	c.-225+33G>A		intron_variant		1		ENSP00000366764.1
PER3	ENST00000614998.4	c.-284G>A		upstream_gene_variant		1		ENSP00000479223.1
PER3	ENST00000613533.4	c.-284G>A		upstream_gene_variant		5		ENSP00000482093.1

Frequencies

GnomAD3 genomes AF: 0.0730 AC: 10967 AN: 150220 Hom.: 508 Cov.: 32

Gnomad AFR AF: 0.0219

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.0687

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.0464

Gnomad SAS AF: 0.0922

Gnomad FIN AF: 0.0698

Gnomad MID AF: 0.126

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0837

GnomAD4 exome AF: 0.0692 AC: 36 AN: 520 Hom.: 2 Cov.: 0 AF XY: 0.0582 AC XY: 22 AN XY: 378

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0625

Gnomad4 SAS exome AF: 0.0750

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0704

Gnomad4 OTH exome AF: 0.150

GnomAD4 genome AF: 0.0729 AC: 10966 AN: 150330 Hom.: 509 Cov.: 32 AF XY: 0.0716 AC XY: 5262 AN XY: 73458

Gnomad4 AFR AF: 0.0219

Gnomad4 AMR AF: 0.0686

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.0464

Gnomad4 SAS AF: 0.0920

Gnomad4 FIN AF: 0.0698

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.0827

Alfa AF: 0.0317 Hom.: 18

Bravo AF: 0.0710

Asia WGS AF: 0.0610 AC: 210 AN: 3436

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.2
DANN	Benign	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs228730; hg19: chr1-7844469;