Variant 17-8142640-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.489

Variant links:

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]

PER1 links:

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ACMG classification

Classification made for transcript

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 GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PER1	NM_002616.3 linkuse as main transcript	c.3259+9C>T		intron_variant		ENST00000317276.9	NP_002607.2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PER1	ENST00000317276.9 linkuse as main transcript	c.3259+9C>T	intron_variant		1	NM_002616.3	ENSP00000314420	P1	O15534-1
PER1	ENST00000581082.5 linkuse as main transcript	c.3190+9C>T	intron_variant		5		ENSP00000462064
PER1	ENST00000579098.1 linkuse as main transcript	n.275C>T	non_coding_transcript_exon_variant	2/2	2
PER1	ENST00000582719.5 linkuse as main transcript	c.*173+9C>T	intron_variant, NMD_transcript_variant		5		ENSP00000463054

Frequencies

GnomAD3 genomes

AF:

0.00535

AC:

814

AN:

152220

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00568

AC XY:

764

AN XY:

134612

show subpopulations

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.:

Cov.:

AF XY:

0.00703

AC XY:

5108

AN XY:

726504

show subpopulations

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.:

Cov.:

AF XY:

0.00510

AC XY:

380

AN XY:

74484

show subpopulations

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.:

Bravo

AF:

0.00493

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00845

EpiControl

AF:

0.0106

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 28, 2018

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over