1-7831023-A-T

Variant names:

• chr1-7831023-A-T
• rs228664
• NM_001377275.1:c.3214+862A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001377275.1(PER3):​c.3214+862A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.966 in 152,332 control chromosomes in the GnomAD database, including 71,159 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 0.97 (71159 hom., cov: 32)
• Consequence: PER3 NM_001377275.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.462
• Publications: 3 publications found

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]

PER3 Gene-Disease associations (from GenCC):

• advanced sleep phase syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PER3	NM_001377275.1	c.3214+862A>T		intron_variant	Intron 19 of 21	ENST00000377532.8	NP_001364204.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PER3	ENST00000377532.8	c.3214+862A>T		intron_variant	Intron 19 of 21	1	NM_001377275.1	ENSP00000366755.3
PER3	ENST00000361923.2	c.3187+862A>T		intron_variant	Intron 18 of 20	1		ENSP00000355031.2
PER3	ENST00000614998.4	c.3157+862A>T		intron_variant	Intron 20 of 22	1		ENSP00000479223.1
PER3	ENST00000613533.4	c.3214+862A>T		intron_variant	Intron 19 of 21	5		ENSP00000482093.1

Frequencies

GnomAD3 genomes AF: 0.966 AC: 147103 AN: 152214 Hom.: 71103 Cov.: 32

Gnomad AFR AF: 0.975

Gnomad AMI AF: 0.888

Gnomad AMR AF: 0.971

Gnomad ASJ AF: 0.976

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.980

Gnomad FIN AF: 0.968

Gnomad MID AF: 0.975

Gnomad NFE AF: 0.957

Gnomad OTH AF: 0.964

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.966 AC: 147218 AN: 152332 Hom.: 71159 Cov.: 32 AF XY: 0.967 AC XY: 72021 AN XY: 74482

African (AFR) AF: 0.975 AC: 40543 AN: 41568

American (AMR) AF: 0.971 AC: 14867 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.976 AC: 3387 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5190 AN: 5190

South Asian (SAS) AF: 0.979 AC: 4729 AN: 4828

European-Finnish (FIN) AF: 0.968 AC: 10272 AN: 10614

Middle Eastern (MID) AF: 0.976 AC: 287 AN: 294

European-Non Finnish (NFE) AF: 0.957 AC: 65091 AN: 68030

Other (OTH) AF: 0.965 AC: 2042 AN: 2116

Alfa AF: 0.963 Hom.: 8771

Bravo AF: 0.967

Asia WGS AF: 0.986 AC: 3430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.30
DANN	Benign	0.72
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs228664; hg19: chr1-7891083;