rs12137927

chr1-7811169-T-C

Variant summary

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

The NM_001377275.1(PER3):c.1522+581T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,142 control chromosomes in the GnomAD database, including 3,194 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 0.20 (3194 hom., cov: 32)
• Consequence: PER3 NM_001377275.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.239

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]

LOC124903833 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PER3	NM_001377275.1	c.1522+581T>C		intron_variant		ENST00000377532.8
LOC124903833	XR_007065450.1	n.508A>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PER3	ENST00000377532.8	c.1522+581T>C		intron_variant		1	NM_001377275.1	A2
	ENST00000451646.1	n.355+320A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30256 AN: 152024 Hom.: 3183 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.199 AC: 30286 AN: 152142 Hom.: 3194 Cov.: 32 AF XY: 0.202 AC XY: 15022 AN XY: 74382

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.264

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.222

Alfa AF: 0.210 Hom.: 443

Bravo AF: 0.188

Asia WGS AF: 0.219 AC: 763 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	4.5
Dann	Benign	0.92

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: rs12137927; hg19: chr1-7871229; COSMIC: COSV62705024; COSMIC: COSV62705024;