17-8144851-T-C

Position:

• chr17-8144851-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002616.3(PER1):​c.2361A>G​(p.Thr787=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 1,581,704 control chromosomes in the GnomAD database, including 516,872 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 0.71 (40428 hom., cov: 32)
  • Exomes 𝑓: 0.81 (476444 hom.)
• Consequence: PER1 NM_002616.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.14

Genes affected

PER1 (HGNC:8845): (period circadian regulator 1) 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 may increase the risk of getting certain cancers. Alternative splicing has been observed in this gene; however, these variants have not been fully described. [provided by RefSeq, Jan 2014]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP7: Synonymous conserved (PhyloP=-3.14 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PER1	NM_002616.3	c.2361A>G	p.Thr787=	synonymous_variant	18/23	ENST00000317276.9	NP_002607.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PER1	ENST00000317276.9	c.2361A>G	p.Thr787=	synonymous_variant	18/23	1	NM_002616.3	ENSP00000314420	P1

Frequencies

GnomAD3 genomes AF: 0.712 AC: 108223 AN: 151898 Hom.: 40427 Cov.: 32

Gnomad AFR AF: 0.561

Gnomad AMI AF: 0.826

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.598

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.862

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.844

Gnomad OTH AF: 0.696

GnomAD3 exomes AF: 0.699 AC: 148567 AN: 212502 Hom.: 56197 AF XY: 0.720 AC XY: 82742 AN XY: 114916

Gnomad AFR exome AF: 0.541

Gnomad AMR exome AF: 0.423

Gnomad ASJ exome AF: 0.603

Gnomad EAS exome AF: 0.295

Gnomad SAS exome AF: 0.765

Gnomad FIN exome AF: 0.858

Gnomad NFE exome AF: 0.841

Gnomad OTH exome AF: 0.731

GnomAD4 exome AF: 0.806 AC: 1152247 AN: 1429688 Hom.: 476444 Cov.: 56 AF XY: 0.807 AC XY: 571466 AN XY: 708558

Gnomad4 AFR exome AF: 0.548

Gnomad4 AMR exome AF: 0.443

Gnomad4 ASJ exome AF: 0.607

Gnomad4 EAS exome AF: 0.292

Gnomad4 SAS exome AF: 0.771

Gnomad4 FIN exome AF: 0.869

Gnomad4 NFE exome AF: 0.853

Gnomad4 OTH exome AF: 0.758

GnomAD4 genome AF: 0.712 AC: 108260 AN: 152016 Hom.: 40428 Cov.: 32 AF XY: 0.710 AC XY: 52729 AN XY: 74302

Gnomad4 AFR AF: 0.561

Gnomad4 AMR AF: 0.576

Gnomad4 ASJ AF: 0.598

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.766

Gnomad4 FIN AF: 0.862

Gnomad4 NFE AF: 0.844

Gnomad4 OTH AF: 0.687

Alfa AF: 0.795 Hom.: 68671

Bravo AF: 0.679

Asia WGS AF: 0.540 AC: 1880 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.60
DANN	Benign	0.76

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: rs2253820; hg19: chr17-8048169; COSMIC: COSV57917094; COSMIC: COSV57917094;