1-7837562-A-T

Position:

• chr1-7837562-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001377275.1(PER3):​c.3549+413A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,304 control chromosomes in the GnomAD database, including 1,239 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 0.10 (1239 hom., cov: 32)
• Consequence: PER3 NM_001377275.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.43

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PER3	NM_001377275.1	c.3549+413A>T		intron_variant		ENST00000377532.8	NP_001364204.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PER3	ENST00000377532.8	c.3549+413A>T		intron_variant		1	NM_001377275.1	ENSP00000366755	A2

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15986 AN: 152186 Hom.: 1240 Cov.: 32

Gnomad AFR AF: 0.0272

Gnomad AMI AF: 0.0538

Gnomad AMR AF: 0.0738

Gnomad ASJ AF: 0.0452

Gnomad EAS AF: 0.0411

Gnomad SAS AF: 0.0436

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.0895

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

GnomAD4 genome AF: 0.105 AC: 15981 AN: 152304 Hom.: 1239 Cov.: 32 AF XY: 0.106 AC XY: 7911 AN XY: 74462

Gnomad4 AFR AF: 0.0271

Gnomad4 AMR AF: 0.0737

Gnomad4 ASJ AF: 0.0452

Gnomad4 EAS AF: 0.0414

Gnomad4 SAS AF: 0.0433

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.152

Gnomad4 OTH AF: 0.0881

Alfa AF: 0.0580 Hom.: 85

Bravo AF: 0.0897

Asia WGS AF: 0.0550 AC: 191 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.054
DANN	Benign	0.32

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

Other links and lift over

dbSNP: rs12741937; hg19: chr1-7897622;