rs2585408

Positions:

• chr17-8140435-C-T

Variant summary

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

The variant allele was found at a frequency of 0.359 in 189,024 control chromosomes in the GnomAD database, including 13,029 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 0.36 (10573 hom., cov: 33)
  • Exomes 𝑓: 0.34 (2456 hom.)
• Consequence: intergenic_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.728

Genes affected

(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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.8140435C>T		intergenic_region
PER1	NM_002616.3	c.*633G>A		downstream_gene_variant		ENST00000317276.9	NP_002607.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PER1	ENST00000317276.9	c.*633G>A		downstream_gene_variant		1	NM_002616.3	ENSP00000314420.4
PER1	ENST00000581082.5	c.*633G>A		downstream_gene_variant		5		ENSP00000462064.1

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55319 AN: 152060 Hom.: 10574 Cov.: 33

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.360

GnomAD4 exome AF: 0.342 AC: 12609 AN: 36846 Hom.: 2456 Cov.: 0 AF XY: 0.343 AC XY: 5883 AN XY: 17144

Gnomad4 AFR exome AF: 0.337

Gnomad4 AMR exome AF: 0.236

Gnomad4 ASJ exome AF: 0.304

Gnomad4 EAS exome AF: 0.137

Gnomad4 SAS exome AF: 0.256

Gnomad4 FIN exome AF: 0.468

Gnomad4 NFE exome AF: 0.414

Gnomad4 OTH exome AF: 0.355

GnomAD4 genome AF: 0.364 AC: 55328 AN: 152178 Hom.: 10573 Cov.: 33 AF XY: 0.359 AC XY: 26736 AN XY: 74410

Gnomad4 AFR AF: 0.328

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.467

Gnomad4 NFE AF: 0.421

Gnomad4 OTH AF: 0.355

Alfa AF: 0.395 Hom.: 16347

Bravo AF: 0.347

Asia WGS AF: 0.178 AC: 624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.6
DANN	Benign	0.58

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2585408; hg19: chr17-8043753;