rs3027172

Positions:

• chr17-8152405-A-G

Variant summary

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

The ENST00000581703.1(PER1):​c.28T>C​(p.Trp10Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,514 control chromosomes in the GnomAD database, including 2,498 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/9 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.17 (2494 hom., cov: 33)
  • Exomes 𝑓: 0.17 (4 hom.)
• Consequence: PER1 ENST00000581703.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.85

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 (MetaRNN=0.0013884604).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PER1	NM_002616.3			upstream_gene_variant		ENST00000317276.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PER1	ENST00000317276.9			upstream_gene_variant		1	NM_002616.3	P1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25504 AN: 152098 Hom.: 2494 Cov.: 33

Gnomad AFR AF: 0.0922

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.0378

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.162

GnomAD3 exomes AF: 0.382 AC: 71 AN: 186 Hom.: 10 AF XY: 0.412 AC XY: 28 AN XY: 68

Gnomad NFE exome AF: 0.385

Gnomad OTH exome AF: 0.250

GnomAD4 exome AF: 0.168 AC: 50 AN: 298 Hom.: 4 Cov.: 0 AF XY: 0.188 AC XY: 26 AN XY: 138

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.269

Gnomad4 NFE exome AF: 0.191

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.168 AC: 25514 AN: 152216 Hom.: 2494 Cov.: 33 AF XY: 0.162 AC XY: 12085 AN XY: 74426

Gnomad4 AFR AF: 0.0922

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.0375

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.160

Alfa AF: 0.192 Hom.: 380

Bravo AF: 0.165

TwinsUK AF: 0.246 AC: 914

ALSPAC AF: 0.234 AC: 903

ExAC AF: 0.0227 AC: 61

Asia WGS AF: 0.0710 AC: 246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	19
DANN	Benign	0.88
DEOGEN2	Benign	0.0084	T
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.12	T
MetaRNN	Benign	0.0014	T
MutationTaster	Benign	2.6e-10	P;P
Sift4G	Benign	0.37	T
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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: rs3027172; hg19: chr17-8055723;