chr17-8147419-G-C

Variant names:

• chr17-8147419-G-C
• rs885747
• NM_002616.3:c.1498-38C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002616.3(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 NM_002616.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90
• Publications: 28 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]

ACMG classification

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PER1	NM_002616.3	MANE Select	c.1498-38C>G		intron	N/A	NP_002607.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PER1	ENST00000317276.9	TSL:1 MANE Select	c.1498-38C>G		intron	N/A	ENSP00000314420.4
	PER1	ENST00000581082.6	TSL:5	c.1438-38C>G		intron	N/A	ENSP00000462064.1
	PER1	ENST00000354903.9	TSL:2	c.1450-38C>G		intron	N/A	ENSP00000346979.5

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

GnomAD2 exomes AF: 0.370 AC: 91478 AN: 247354 AF XY: 0.368

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 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

African (AFR) AF: 0.559 AC: 18692 AN: 33462

American (AMR) AF: 0.219 AC: 9787 AN: 44614

Ashkenazi Jewish (ASJ) AF: 0.373 AC: 9735 AN: 26074

East Asian (EAS) AF: 0.129 AC: 5103 AN: 39652

South Asian (SAS) AF: 0.284 AC: 24477 AN: 86204

European-Finnish (FIN) AF: 0.495 AC: 26326 AN: 53166

Middle Eastern (MID) AF: 0.345 AC: 1991 AN: 5764

European-Non Finnish (NFE) AF: 0.437 AC: 485490 AN: 1110600

Other (OTH) AF: 0.403 AC: 24314 AN: 60296

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

African (AFR) AF: 0.558 AC: 23077 AN: 41386

American (AMR) AF: 0.311 AC: 4755 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1288 AN: 3468

East Asian (EAS) AF: 0.118 AC: 608 AN: 5166

South Asian (SAS) AF: 0.265 AC: 1278 AN: 4818

European-Finnish (FIN) AF: 0.504 AC: 5322 AN: 10564

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.441 AC: 29912 AN: 67902

Other (OTH) AF: 0.417 AC: 880 AN: 2112

Alfa AF: 0.340 Hom.: 1417

Bravo AF: 0.435

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.015
DANN	Benign	0.41
PhyloP100		-1.9
Mutation Taster		=100/0	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: rs885747; hg19: chr17-8050737; COSMIC: COSV57917101; COSMIC: COSV57917101;