17-8144851-T-C

Variant names:

• chr17-8144851-T-C
• rs2253820
• NM_002616.3:c.2361A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002616.3(PER1):​c.2361A>G​(p.Thr787Thr) 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
• Publications: 52 publications found

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]

MIR6883 (HGNC:50019): (microRNA 6883) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002616.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PER1	NM_002616.3	MANE Select	c.2361A>G	p.Thr787Thr	synonymous	Exon 18 of 23	NP_002607.2
	MIR6883	NR_106943.1		n.*143A>G		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PER1	ENST00000317276.9	TSL:1 MANE Select	c.2361A>G	p.Thr787Thr	synonymous	Exon 18 of 23	ENSP00000314420.4
	PER1	ENST00000857860.1		c.2361A>G	p.Thr787Thr	synonymous	Exon 18 of 23	ENSP00000527919.1
	PER1	ENST00000857861.1		c.2358A>G	p.Thr786Thr	synonymous	Exon 18 of 23	ENSP00000527920.1

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

GnomAD2 exomes AF: 0.699 AC: 148567 AN: 212502 AF XY: 0.720

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 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

African (AFR) AF: 0.548 AC: 18024 AN: 32898

American (AMR) AF: 0.443 AC: 18383 AN: 41542

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 15048 AN: 24810

East Asian (EAS) AF: 0.292 AC: 11274 AN: 38562

South Asian (SAS) AF: 0.771 AC: 63184 AN: 81996

European-Finnish (FIN) AF: 0.869 AC: 44284 AN: 50950

Middle Eastern (MID) AF: 0.654 AC: 3697 AN: 5656

European-Non Finnish (NFE) AF: 0.853 AC: 933674 AN: 1094338

Other (OTH) AF: 0.758 AC: 44679 AN: 58936

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

African (AFR) AF: 0.561 AC: 23223 AN: 41428

American (AMR) AF: 0.576 AC: 8814 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.598 AC: 2073 AN: 3468

East Asian (EAS) AF: 0.306 AC: 1575 AN: 5154

South Asian (SAS) AF: 0.766 AC: 3686 AN: 4810

European-Finnish (FIN) AF: 0.862 AC: 9126 AN: 10586

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.844 AC: 57377 AN: 67966

Other (OTH) AF: 0.687 AC: 1449 AN: 2108

Alfa AF: 0.789 Hom.: 89286

Bravo AF: 0.679

Asia WGS AF: 0.540 AC: 1880 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.60
DANN	Benign	0.76
PhyloP100		-3.1
Mutation Taster		=75/25	polymorphism (auto)

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

Other links and lift over

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