Variant rs2735611 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_002616.3(PER1):c.2247C>T(p.Gly749Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.802 in 1,502,102 control chromosomes in the GnomAD database, including 495,548 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 0.71 ( 40429 hom., cov: 31)

Exomes 𝑓: 0.81 ( 455119 hom. )

Consequence

PER1
NM_002616.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.386

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:

MIR6883 (HGNC:50019): (microRNA 6883) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR6883 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP7

Synonymous conserved (PhyloP=0.386 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PER1	NM_002616.3 link	c.2247C>T	p.Gly749Gly	synonymous_variant	18/23	ENST00000317276.9	NP_002607.2	O15534-1
MIR6883	NR_106943.1 link	n.*29C>T		downstream_gene_variant
MIR6883	unassigned_transcript_2947	n.*29C>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PER1	ENST00000317276.9 link	c.2247C>T	p.Gly749Gly	synonymous_variant	18/23	1	NM_002616.3	ENSP00000314420.4		O15534-1

Frequencies

GnomAD3 genomes

AF:

0.712

AC:

108213

AN:

151892

Hom.:

40429

Cov.:

show subpopulations

Gnomad AFR

AF:

0.561

Gnomad AMI

AF:

0.825

Gnomad AMR

AF:

0.577

Gnomad ASJ

AF:

0.598

Gnomad EAS

AF:

0.305

Gnomad SAS

AF:

0.763

Gnomad FIN

AF:

0.862

Gnomad MID

AF:

0.620

Gnomad NFE

AF:

0.844

Gnomad OTH

AF:

0.696

GnomAD3 exomes

AF:

0.710

AC:

116576

AN:

164202

Hom.:

44744

AF XY:

0.729

AC XY:

64054

AN XY:

87892

show subpopulations

Gnomad AFR exome

AF:

0.544

Gnomad AMR exome

AF:

0.438

Gnomad ASJ exome

AF:

0.598

Gnomad EAS exome

AF:

0.293

Gnomad SAS exome

AF:

0.762

Gnomad FIN exome

AF:

0.861

Gnomad NFE exome

AF:

0.845

Gnomad OTH exome

AF:

0.741

GnomAD4 exome

AF:

0.812

AC:

1095729

AN:

1350092

Hom.:

455119

Cov.:

AF XY:

0.812

AC XY:

536805

AN XY:

661350

show subpopulations

Gnomad4 AFR exome

AF:

0.548

Gnomad4 AMR exome

AF:

0.460

Gnomad4 ASJ exome

AF:

0.607

Gnomad4 EAS exome

AF:

0.292

Gnomad4 SAS exome

AF:

0.770

Gnomad4 FIN exome

AF:

0.870

Gnomad4 NFE exome

AF:

0.854

Gnomad4 OTH exome

AF:

0.765

GnomAD4 genome

AF:

0.712

AC:

108248

AN:

152010

Hom.:

40429

Cov.:

AF XY:

0.710

AC XY:

52730

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.561

Gnomad4 AMR

AF:

0.577

Gnomad4 ASJ

AF:

0.598

Gnomad4 EAS

AF:

0.304

Gnomad4 SAS

AF:

0.765

Gnomad4 FIN

AF:

0.862

Gnomad4 NFE

AF:

0.844

Gnomad4 OTH

AF:

0.687

Alfa

AF:

0.789

Hom.:

47158

Bravo

AF:

0.679

Asia WGS

AF:

0.533

AC:

1855

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

5.8

DANN

Benign

0.76

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

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