17-8153288-T-G

Variant summary

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

The ENST00000354903.9(PER1):c.49-2678A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.853 in 152,130 control chromosomes in the GnomAD database, including 55,865 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 0.85 (55865 hom., cov: 32)
• Consequence: PER1 ENST00000354903.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.293

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PER1	ENST00000354903.9	c.49-2678A>C		intron_variant		2
PER1	ENST00000577253.5	c.-139-2443A>C		intron_variant		4
PER1	ENST00000584202.1	c.-140+642A>C		intron_variant		5
PER1	ENST00000581395.5	c.-139-2443A>C		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.853 AC: 129664 AN: 152012 Hom.: 55837 Cov.: 32

Gnomad AFR AF: 0.785

Gnomad AMI AF: 0.837

Gnomad AMR AF: 0.855

Gnomad ASJ AF: 0.732

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.874

Gnomad FIN AF: 0.933

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.911

Gnomad OTH AF: 0.834

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

GnomAD4 genome AF: 0.853 AC: 129743 AN: 152130 Hom.: 55865 Cov.: 32 AF XY: 0.853 AC XY: 63463 AN XY: 74378

Gnomad4 AFR AF: 0.785

Gnomad4 AMR AF: 0.855

Gnomad4 ASJ AF: 0.732

Gnomad4 EAS AF: 0.537

Gnomad4 SAS AF: 0.875

Gnomad4 FIN AF: 0.933

Gnomad4 NFE AF: 0.911

Gnomad4 OTH AF: 0.831

Alfa AF: 0.893 Hom.: 83386

Bravo AF: 0.840

Asia WGS AF: 0.732 AC: 2545 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	6.7
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: rs2518023; hg19: chr17-8056606;