17-8142640-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002616.3(PER1):c.3259+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00703 in 1,613,094 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0053 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0072 (45 hom.)
• Consequence: PER1 NM_002616.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.489

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 17-8142640-G-A is Benign according to our data. Variant chr17-8142640-G-A is described in ClinVar as [Benign]. Clinvar id is 771764.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PER1	NM_002616.3	c.3259+9C>T		intron_variant		ENST00000317276.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PER1	ENST00000317276.9	c.3259+9C>T		intron_variant		1	NM_002616.3	P1
PER1	ENST00000581082.5	c.3190+9C>T		intron_variant		5
PER1	ENST00000579098.1	n.275C>T		non_coding_transcript_exon_variant	2/2	2
PER1	ENST00000582719.5	c.*173+9C>T		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00535 AC: 814 AN: 152220 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00150

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00641

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00574

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00842

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00564 AC: 1404 AN: 248796 Hom.: 7 AF XY: 0.00568 AC XY: 764 AN XY: 134612

Gnomad AFR exome AF: 0.00123

Gnomad AMR exome AF: 0.00434

Gnomad ASJ exome AF: 0.00408

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000294

Gnomad FIN exome AF: 0.00689

Gnomad NFE exome AF: 0.00895

Gnomad OTH exome AF: 0.00639

GnomAD4 exome AF: 0.00721 AC: 10528 AN: 1460756 Hom.: 45 Cov.: 34 AF XY: 0.00703 AC XY: 5108 AN XY: 726504

Gnomad4 AFR exome AF: 0.00120

Gnomad4 AMR exome AF: 0.00439

Gnomad4 ASJ exome AF: 0.00306

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000232

Gnomad4 FIN exome AF: 0.00730

Gnomad4 NFE exome AF: 0.00847

Gnomad4 OTH exome AF: 0.00640

GnomAD4 genome AF: 0.00535 AC: 815 AN: 152338 Hom.: 3 Cov.: 32 AF XY: 0.00510 AC XY: 380 AN XY: 74484

Gnomad4 AFR AF: 0.00149

Gnomad4 AMR AF: 0.00640

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00574

Gnomad4 NFE AF: 0.00842

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.00625 Hom.: 2

Bravo AF: 0.00493

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00845

EpiControl AF: 0.0106

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 28, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	3.6
Dann	Benign	0.94

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs146151077; hg19: chr17-8045958; COSMIC: COSV57920229; COSMIC: COSV57920229;