rs2797687

Variant names:

• chr1-7784383-G-T
• rs2797687
• NM_001377275.1:c.-225+7G>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.-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
• Publications: 5 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377275.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PER3	NM_001377275.1	MANE Select	c.-225+7G>T		splice_region intron	N/A	NP_001364204.1	P56645-2
	PER3	NM_016831.4		c.-310G>T		5_prime_UTR	Exon 1 of 22	NP_058515.1	A2I2N5
	PER3	NM_001289861.2		c.-310G>T		5_prime_UTR	Exon 1 of 23	NP_001276790.1	A0A087WV69

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PER3	ENST00000377532.8	TSL:1 MANE Select	c.-225+7G>T		splice_region intron	N/A	ENSP00000366755.3	P56645-2
	PER3	ENST00000377541.5	TSL:1	c.-225+7G>T		splice_region intron	N/A	ENSP00000366764.1	Q8TAR6
	PER3	ENST00000961537.1		c.-495G>T		5_prime_UTR	Exon 1 of 21	ENSP00000631596.1

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

African (AFR) AF: 0.500 AC: 5 AN: 10

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 1 AN: 4

East Asian (EAS) AF: 0.222 AC: 4 AN: 18

South Asian (SAS) AF: 0.142 AC: 15 AN: 106

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.100 AC: 38 AN: 380

Other (OTH) AF: 0.0833 AC: 1 AN: 12

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

African (AFR) AF: 0.333 AC: 13667 AN: 41102

American (AMR) AF: 0.164 AC: 2486 AN: 15140

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 813 AN: 3458

East Asian (EAS) AF: 0.385 AC: 1952 AN: 5072

South Asian (SAS) AF: 0.288 AC: 1379 AN: 4784

European-Finnish (FIN) AF: 0.0616 AC: 634 AN: 10286

Middle Eastern (MID) AF: 0.197 AC: 57 AN: 290

European-Non Finnish (NFE) AF: 0.173 AC: 11537 AN: 66592

Other (OTH) AF: 0.220 AC: 455 AN: 2072

Alfa AF: 0.212 Hom.: 345

Bravo AF: 0.232

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.2
DANN	Benign	0.68
PhyloP100		-0.86
PromoterAI		-0.087	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2797687; hg19: chr1-7844443;