Variant 17-8143454-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002616.3(PER1):c.2884G>C(p.Ala962Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.885 in 1,607,814 control chromosomes in the GnomAD database, including 633,196 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.85 ( 55933 hom., cov: 29)

Exomes 𝑓: 0.89 ( 577263 hom. )

Consequence

PER1
NM_002616.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.553

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.1891894E-6).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PER1	NM_002616.3 link	c.2884G>C	p.Ala962Pro	missense_variant	19/23	ENST00000317276.9	NP_002607.2	O15534-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PER1	ENST00000317276.9 link	c.2884G>C	p.Ala962Pro	missense_variant	19/23	1	NM_002616.3	ENSP00000314420.4	O15534-1
PER1	ENST00000581082.5 link	c.2815G>C	p.Ala939Pro	missense_variant	18/22	5		ENSP00000462064.1	J3KRL7
PER1	ENST00000578089.1 link	n.817G>C		non_coding_transcript_exon_variant	4/4	3
PER1	ENST00000582719.5 link	n.2462-619G>C		intron_variant		5		ENSP00000463054.1	J3KTM2

Frequencies

GnomAD3 genomes

AF:

0.855

AC:

129750

AN:

151820

Hom.:

55898

Cov.:

show subpopulations

Gnomad AFR

AF:

0.803

Gnomad AMI

AF:

0.840

Gnomad AMR

AF:

0.851

Gnomad ASJ

AF:

0.736

Gnomad EAS

AF:

0.540

Gnomad SAS

AF:

0.882

Gnomad FIN

AF:

0.932

Gnomad MID

AF:

0.778

Gnomad NFE

AF:

0.904

Gnomad OTH

AF:

0.825

GnomAD3 exomes

AF:

0.850

AC:

207710

AN:

244436

Hom.:

89614

AF XY:

0.855

AC XY:

113158

AN XY:

132396

show subpopulations

Gnomad AFR exome

AF:

0.794

Gnomad AMR exome

AF:

0.836

Gnomad ASJ exome

AF:

0.749

Gnomad EAS exome

AF:

0.520

Gnomad SAS exome

AF:

0.882

Gnomad FIN exome

AF:

0.927

Gnomad NFE exome

AF:

0.902

Gnomad OTH exome

AF:

0.851

GnomAD4 exome

AF:

0.888

AC:

1292523

AN:

1455878

Hom.:

577263

Cov.:

AF XY:

0.888

AC XY:

642495

AN XY:

723872

show subpopulations

Gnomad4 AFR exome

AF:

0.797

Gnomad4 AMR exome

AF:

0.836

Gnomad4 ASJ exome

AF:

0.751

Gnomad4 EAS exome

AF:

0.554

Gnomad4 SAS exome

AF:

0.882

Gnomad4 FIN exome

AF:

0.932

Gnomad4 NFE exome

AF:

0.908

Gnomad4 OTH exome

AF:

0.858

GnomAD4 genome

AF:

0.855

AC:

129840

AN:

151936

Hom.:

55933

Cov.:

AF XY:

0.855

AC XY:

63504

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.803

Gnomad4 AMR

AF:

0.850

Gnomad4 ASJ

AF:

0.736

Gnomad4 EAS

AF:

0.540

Gnomad4 SAS

AF:

0.883

Gnomad4 FIN

AF:

0.932

Gnomad4 NFE

AF:

0.904

Gnomad4 OTH

AF:

0.822

Alfa

AF:

0.863

Hom.:

10589

Bravo

AF:

0.841

TwinsUK

AF:

0.905

AC:

3354

ALSPAC

AF:

0.909

AC:

3503

ESP6500AA

AF:

0.786

AC:

3460

ESP6500EA

AF:

0.897

AC:

7713

ExAC

AF:

0.851

AC:

103194

Asia WGS

AF:

0.736

AC:

2562

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.044

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.75

CADD

Benign

4.9

DANN

Benign

0.58

DEOGEN2

Benign

0.048

T;T

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.086

T;T

MetaRNN

Benign

0.0000012

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.7

N;.

PrimateAI

Benign

0.43

PROVEAN

Benign

1.3

N;.

REVEL

Benign

0.030

Sift

Benign

0.58

T;.

Sift4G

Benign

0.37

T;T

Polyphen

0.0

B;.

Vest4

0.16

MPC

0.17

ClinPred

0.0024

GERP RS

3.2

Varity_R

0.066

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over