17-8153288-T-G

Variant names:

• chr17-8153288-T-G
• rs2518023
• ENST00000498285.1:c.335-2443A>C

Variant summary

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

The ENST00000498285.1(ENSG00000263620):​c.335-2443A>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: ENSG00000263620 ENST00000498285.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.293
• Publications: 22 publications found

Genes affected

ENSG00000263620 (HGNC:):

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000498285.1. 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000263620	ENST00000498285.1	TSL:4	c.335-2443A>C		intron	N/A	ENSP00000464383.1
	PER1	ENST00000354903.9	TSL:2	c.49-2678A>C		intron	N/A	ENSP00000346979.5
	PER1	ENST00000577253.5	TSL:4	c.-139-2443A>C		intron	N/A	ENSP00000462546.1

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

African (AFR) AF: 0.785 AC: 32547 AN: 41464

American (AMR) AF: 0.855 AC: 13063 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.732 AC: 2542 AN: 3472

East Asian (EAS) AF: 0.537 AC: 2778 AN: 5170

South Asian (SAS) AF: 0.875 AC: 4215 AN: 4816

European-Finnish (FIN) AF: 0.933 AC: 9898 AN: 10610

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.911 AC: 61944 AN: 67998

Other (OTH) AF: 0.831 AC: 1757 AN: 2114

Alfa AF: 0.882 Hom.: 200943

Bravo AF: 0.840

Asia WGS AF: 0.732 AC: 2545 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.7
DANN	Benign	0.76
PhyloP100		-0.29
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: rs2518023; hg19: chr17-8056606;