rs2289591

Variant names:

• chr17-8144692-C-A
• rs2289591
• NM_002616.3:c.2461+59G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-8144692-C-A
• chr17-8144692-C-G
• chr17-8144692-C-T

Variant summary

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

The NM_002616.3(PER1):​c.2461+59G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 1,535,698 control chromosomes in the GnomAD database, including 41,028 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 0.16 (2728 hom., cov: 32)
  • Exomes 𝑓: 0.23 (38300 hom.)
• Consequence: PER1 NM_002616.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.679
• Publications: 33 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 (MetaRNN=0.004916042).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PER1	NM_002616.3	c.2461+59G>T		intron_variant	Intron 18 of 22	ENST00000317276.9	NP_002607.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PER1	ENST00000317276.9	c.2461+59G>T		intron_variant	Intron 18 of 22	1	NM_002616.3	ENSP00000314420.4

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25104 AN: 152116 Hom.: 2729 Cov.: 32

Gnomad AFR AF: 0.0441

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.0358

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.171

GnomAD2 exomes AF: 0.169 AC: 23486 AN: 138940 AF XY: 0.174

Gnomad AFR exome AF: 0.0385

Gnomad AMR exome AF: 0.109

Gnomad ASJ exome AF: 0.226

Gnomad EAS exome AF: 0.0437

Gnomad FIN exome AF: 0.188

Gnomad NFE exome AF: 0.245

Gnomad OTH exome AF: 0.209

GnomAD4 exome AF: 0.227 AC: 313445 AN: 1383464 Hom.: 38300 Cov.: 29 AF XY: 0.224 AC XY: 153293 AN XY: 682920

African (AFR) AF: 0.0341 AC: 1078 AN: 31568

American (AMR) AF: 0.116 AC: 4145 AN: 35686

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 5727 AN: 25122

East Asian (EAS) AF: 0.0277 AC: 989 AN: 35742

South Asian (SAS) AF: 0.127 AC: 10076 AN: 79050

European-Finnish (FIN) AF: 0.188 AC: 6715 AN: 35784

Middle Eastern (MID) AF: 0.189 AC: 1078 AN: 5694

European-Non Finnish (NFE) AF: 0.252 AC: 271866 AN: 1076972

Other (OTH) AF: 0.203 AC: 11771 AN: 57846

GnomAD4 genome AF: 0.165 AC: 25098 AN: 152234 Hom.: 2728 Cov.: 32 AF XY: 0.160 AC XY: 11914 AN XY: 74438

African (AFR) AF: 0.0440 AC: 1826 AN: 41546

American (AMR) AF: 0.150 AC: 2292 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 800 AN: 3470

East Asian (EAS) AF: 0.0353 AC: 183 AN: 5188

South Asian (SAS) AF: 0.114 AC: 549 AN: 4830

European-Finnish (FIN) AF: 0.177 AC: 1875 AN: 10616

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.249 AC: 16930 AN: 67960

Other (OTH) AF: 0.169 AC: 357 AN: 2114

Alfa AF: 0.213 Hom.: 5047

Bravo AF: 0.159

TwinsUK AF: 0.264 AC: 980

ALSPAC AF: 0.254 AC: 979

ExAC AF: 0.105 AC: 10226

Asia WGS AF: 0.0700 AC: 241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.20
DANN	Benign	0.51
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.23	T
MetaRNN	Benign	0.0049	T
MetaSVM	Benign	-0.98	T
PhyloP100		-0.68
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.016
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.19	T
Vest4		0.22
MutPred		0.27		Gain of ubiquitination at K829 (P = 0.0418);
ClinPred		0.00078	T
GERP RS		-3.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs2289591; hg19: chr17-8048010; COSMIC: COSV57917166; COSMIC: COSV57917166;