chr17-8145667-G-C

Position:

• chr17-8145667-G-C

Variant summary

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

The NM_002616.3(PER1):​c.2218+291C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 152,084 control chromosomes in the GnomAD database, including 43,383 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 0.74 (43383 hom., cov: 31)
• Consequence: PER1 NM_002616.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.168

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]

PER1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PER1	NM_002616.3	c.2218+291C>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.2218+291C>G		intron_variant		1	NM_002616.3	ENSP00000314420.4

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112626 AN: 151968 Hom.: 43372 Cov.: 31

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.826

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.796

Gnomad FIN AF: 0.892

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.857

Gnomad OTH AF: 0.715

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

GnomAD4 genome AF: 0.741 AC: 112680 AN: 152084 Hom.: 43383 Cov.: 31 AF XY: 0.739 AC XY: 54947 AN XY: 74366

Gnomad4 AFR AF: 0.624

Gnomad4 AMR AF: 0.592

Gnomad4 ASJ AF: 0.634

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.798

Gnomad4 FIN AF: 0.892

Gnomad4 NFE AF: 0.857

Gnomad4 OTH AF: 0.706

Alfa AF: 0.798 Hom.: 6173

Bravo AF: 0.706

Asia WGS AF: 0.578 AC: 2011 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.40

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: rs3027188; hg19: chr17-8048985;