1-7819567-C-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001377275.1(PER3):​c.1658+147C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00326 in 688,198 control chromosomes in the GnomAD database, including 15 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 0.0030 ( 2 hom., cov: 33)
Exomes 𝑓: 0.0033 ( 13 hom. )

Consequence

PER3
NM_001377275.1 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.14
Variant links:
Genes affected
PER3 (HGNC:8847): (period circadian regulator 3) 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 have been linked to sleep disorders. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2014]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BS2
High AC in GnomAd4 at 456 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PER3NM_001377275.1 linkc.1658+147C>G intron_variant Intron 14 of 21 ENST00000377532.8 NP_001364204.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PER3ENST00000377532.8 linkc.1658+147C>G intron_variant Intron 14 of 21 1 NM_001377275.1 ENSP00000366755.3 P56645-2

Frequencies

GnomAD3 genomes
AF:
0.00300
AC:
456
AN:
152032
Hom.:
2
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000218
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000459
Gnomad ASJ
AF:
0.00691
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.0174
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00334
Gnomad OTH
AF:
0.00191
GnomAD4 exome
AF:
0.00334
AC:
1788
AN:
536048
Hom.:
13
AF XY:
0.00318
AC XY:
908
AN XY:
285402
show subpopulations
Gnomad4 AFR exome
AF:
0.000345
Gnomad4 AMR exome
AF:
0.000121
Gnomad4 ASJ exome
AF:
0.00786
Gnomad4 EAS exome
AF:
0.0000290
Gnomad4 SAS exome
AF:
0.000744
Gnomad4 FIN exome
AF:
0.0183
Gnomad4 NFE exome
AF:
0.00270
Gnomad4 OTH exome
AF:
0.00331
GnomAD4 genome
AF:
0.00300
AC:
456
AN:
152150
Hom.:
2
Cov.:
33
AF XY:
0.00360
AC XY:
268
AN XY:
74362
show subpopulations
Gnomad4 AFR
AF:
0.000217
Gnomad4 AMR
AF:
0.000458
Gnomad4 ASJ
AF:
0.00691
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.0174
Gnomad4 NFE
AF:
0.00334
Gnomad4 OTH
AF:
0.00189
Alfa
AF:
0.000213
Hom.:
3040

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
0.21
DANN
Benign
0.44

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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.

Other links and lift over

dbSNP: rs10462018; hg19: chr1-7879627; API