rs3027188

Variant names:

• chr17-8145667-G-C
• rs3027188
• NM_002616.3:c.2218+291C>G

Variant summary

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

The NM_002616.3(PER1):​c.2218+291C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 152,084 control chromosomes in the GnomAD database, including 43,383 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 0.74 (43383 hom., cov: 31)
• Consequence: PER1 NM_002616.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.168
• Publications: 18 publications found

Genes affected

PER1 (HGNC:8845): (period circadian regulator 1) 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 may increase the risk of getting certain cancers. Alternative splicing has been observed in this gene; however, these variants have not been fully described. [provided by RefSeq, Jan 2014]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002616.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PER1	NM_002616.3	MANE Select	c.2218+291C>G		intron	N/A	NP_002607.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PER1	ENST00000317276.9	TSL:1 MANE Select	c.2218+291C>G		intron	N/A	ENSP00000314420.4
	PER1	ENST00000585095.2	TSL:3	n.1664C>G		non_coding_transcript_exon	Exon 3 of 3
	PER1	ENST00000581082.6	TSL:5	c.2158+291C>G		intron	N/A	ENSP00000462064.1

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112626 AN: 151968 Hom.: 43372 Cov.: 31

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.826

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.796

Gnomad FIN AF: 0.892

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.857

Gnomad OTH AF: 0.715

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

GnomAD4 genome AF: 0.741 AC: 112680 AN: 152084 Hom.: 43383 Cov.: 31 AF XY: 0.739 AC XY: 54947 AN XY: 74366

African (AFR) AF: 0.624 AC: 25881 AN: 41452

American (AMR) AF: 0.592 AC: 9036 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.634 AC: 2199 AN: 3470

East Asian (EAS) AF: 0.306 AC: 1575 AN: 5150

South Asian (SAS) AF: 0.798 AC: 3853 AN: 4830

European-Finnish (FIN) AF: 0.892 AC: 9457 AN: 10602

Middle Eastern (MID) AF: 0.682 AC: 199 AN: 292

European-Non Finnish (NFE) AF: 0.857 AC: 58237 AN: 67990

Other (OTH) AF: 0.706 AC: 1490 AN: 2110

Alfa AF: 0.798 Hom.: 6173

Bravo AF: 0.706

Asia WGS AF: 0.578 AC: 2011 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.40
PhyloP100		-0.17
PromoterAI		-0.0040	Neutral
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: rs3027188; hg19: chr17-8048985;