chr1-7792859-T-C

Position:

• chr1-7792859-T-C

Variant summary

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

The ENST00000377532.8(PER3):​c.593-1098T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,248 control chromosomes in the GnomAD database, including 1,602 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 0.13 (1602 hom., cov: 32)
• Consequence: PER3 ENST00000377532.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.258

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PER3	NM_001377275.1	c.593-1098T>C		intron_variant		ENST00000377532.8	NP_001364204.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PER3	ENST00000377532.8	c.593-1098T>C		intron_variant		1	NM_001377275.1	ENSP00000366755	A2

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20151 AN: 152130 Hom.: 1602 Cov.: 32

Gnomad AFR AF: 0.0560

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.0108

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.132 AC: 20168 AN: 152248 Hom.: 1602 Cov.: 32 AF XY: 0.133 AC XY: 9895 AN XY: 74420

Gnomad4 AFR AF: 0.0561

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.0108

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.129

Alfa AF: 0.161 Hom.: 1210

Bravo AF: 0.126

Asia WGS AF: 0.0570 AC: 196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.4
DANN	Benign	0.61

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: rs875994; hg19: chr1-7852919;