chr1-7784383-G-T

Position:

• chr1-7784383-G-T

Variant summary

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

The NM_001377275.1(PER3):​c.-225+7G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 150,184 control chromosomes in the GnomAD database, including 4,280 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.22 (4277 hom., cov: 31)
  • Exomes 𝑓: 0.12 (3 hom.)
• Consequence: PER3 NM_001377275.1 splice_region, intron
• Scores: Splicing: ADA: 0.00007859
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.862

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PER3	NM_001377275.1	c.-225+7G>T		splice_region_variant, intron_variant		ENST00000377532.8	NP_001364204.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PER3	ENST00000377532.8	c.-225+7G>T		splice_region_variant, intron_variant		1	NM_001377275.1	ENSP00000366755	A2
PER3	ENST00000377541.5	c.-225+7G>T		splice_region_variant, intron_variant		1		ENSP00000366764
PER3	ENST00000614998.4			upstream_gene_variant		1		ENSP00000479223	A2
PER3	ENST00000613533.4			upstream_gene_variant		5		ENSP00000482093	A2

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33076 AN: 149536 Hom.: 4276 Cov.: 31

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.0616

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.220

GnomAD4 exome AF: 0.120 AC: 64 AN: 534 Hom.: 3 Cov.: 0 AF XY: 0.115 AC XY: 45 AN XY: 390

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.222

Gnomad4 SAS exome AF: 0.142

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.100

Gnomad4 OTH exome AF: 0.0833

GnomAD4 genome AF: 0.221 AC: 33100 AN: 149650 Hom.: 4277 Cov.: 31 AF XY: 0.216 AC XY: 15821 AN XY: 73290

Gnomad4 AFR AF: 0.333

Gnomad4 AMR AF: 0.164

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.385

Gnomad4 SAS AF: 0.288

Gnomad4 FIN AF: 0.0616

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.220

Alfa AF: 0.212 Hom.: 345

Bravo AF: 0.232

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.2
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000079
dbscSNV1_RF	Benign	0.038

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2797687; hg19: chr1-7844443;