chr17-8147419-G-C

Position:

• chr17-8147419-G-C

Variant summary

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

The ENST00000317276.9(PER1):​c.1498-38C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 1,611,724 control chromosomes in the GnomAD database, including 146,524 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 0.45 (15919 hom., cov: 31)
  • Exomes 𝑓: 0.42 (130605 hom.)
• Consequence: PER1 ENST00000317276.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PER1	NM_002616.3	c.1498-38C>G		intron_variant		ENST00000317276.9	NP_002607.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PER1	ENST00000317276.9	c.1498-38C>G		intron_variant		1	NM_002616.3	ENSP00000314420	P1

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67552 AN: 151774 Hom.: 15911 Cov.: 31

Gnomad AFR AF: 0.558

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.422

GnomAD3 exomes AF: 0.370 AC: 91478 AN: 247354 Hom.: 18930 AF XY: 0.368 AC XY: 49339 AN XY: 134062

Gnomad AFR exome AF: 0.554

Gnomad AMR exome AF: 0.205

Gnomad ASJ exome AF: 0.373

Gnomad EAS exome AF: 0.106

Gnomad SAS exome AF: 0.281

Gnomad FIN exome AF: 0.498

Gnomad NFE exome AF: 0.438

Gnomad OTH exome AF: 0.379

GnomAD4 exome AF: 0.415 AC: 605915 AN: 1459832 Hom.: 130605 Cov.: 44 AF XY: 0.411 AC XY: 298344 AN XY: 725964

Gnomad4 AFR exome AF: 0.559

Gnomad4 AMR exome AF: 0.219

Gnomad4 ASJ exome AF: 0.373

Gnomad4 EAS exome AF: 0.129

Gnomad4 SAS exome AF: 0.284

Gnomad4 FIN exome AF: 0.495

Gnomad4 NFE exome AF: 0.437

Gnomad4 OTH exome AF: 0.403

GnomAD4 genome AF: 0.445 AC: 67594 AN: 151892 Hom.: 15919 Cov.: 31 AF XY: 0.439 AC XY: 32537 AN XY: 74200

Gnomad4 AFR AF: 0.558

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.371

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.504

Gnomad4 NFE AF: 0.441

Gnomad4 OTH AF: 0.417

Alfa AF: 0.340 Hom.: 1417

Bravo AF: 0.435

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.015
DANN	Benign	0.41

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: rs885747; hg19: chr17-8050737; COSMIC: COSV57917101; COSMIC: COSV57917101;