rs2304911

Positions:

• chr17-8147661-A-G

Variant summary

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

The NM_002616.3(PER1):​c.1388+13T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.071 in 1,613,792 control chromosomes in the GnomAD database, including 8,706 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 0.099 (1242 hom., cov: 33)
  • Exomes 𝑓: 0.068 (7464 hom.)
• Consequence: PER1 NM_002616.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37

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=-0.75).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PER1	NM_002616.3	c.1388+13T>C		intron_variant		ENST00000317276.9	NP_002607.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PER1	ENST00000317276.9	c.1388+13T>C		intron_variant		1	NM_002616.3	ENSP00000314420	P1

Frequencies

GnomAD3 genomes AF: 0.0988 AC: 15022 AN: 152118 Hom.: 1231 Cov.: 33

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.0399

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0479

Gnomad OTH AF: 0.0982

GnomAD3 exomes AF: 0.123 AC: 30875 AN: 250524 Hom.: 3979 AF XY: 0.112 AC XY: 15156 AN XY: 135466

Gnomad AFR exome AF: 0.124

Gnomad AMR exome AF: 0.393

Gnomad ASJ exome AF: 0.105

Gnomad EAS exome AF: 0.225

Gnomad SAS exome AF: 0.119

Gnomad FIN exome AF: 0.0370

Gnomad NFE exome AF: 0.0447

Gnomad OTH exome AF: 0.102

GnomAD4 exome AF: 0.0681 AC: 99490 AN: 1461556 Hom.: 7464 Cov.: 35 AF XY: 0.0680 AC XY: 49425 AN XY: 727052

Gnomad4 AFR exome AF: 0.127

Gnomad4 AMR exome AF: 0.377

Gnomad4 ASJ exome AF: 0.107

Gnomad4 EAS exome AF: 0.264

Gnomad4 SAS exome AF: 0.116

Gnomad4 FIN exome AF: 0.0351

Gnomad4 NFE exome AF: 0.0431

Gnomad4 OTH exome AF: 0.0808

GnomAD4 genome AF: 0.0989 AC: 15059 AN: 152236 Hom.: 1242 Cov.: 33 AF XY: 0.103 AC XY: 7689 AN XY: 74428

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.251

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.0399

Gnomad4 NFE AF: 0.0479

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0658 Hom.: 1348

Bravo AF: 0.116

Asia WGS AF: 0.196 AC: 680 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	9.2
DANN	Benign	0.71

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: rs2304911; hg19: chr17-8050979; COSMIC: COSV57919131; COSMIC: COSV57919131;