rs146151077

Variant names:

• chr17-8142640-G-A
• rs146151077
• NM_002616.3:c.3259+9C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-8142640-G-A
• chr17-8142640-G-C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002616.3(PER1):​c.3259+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00703 in 1,613,094 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0053 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0072 (45 hom.)
• Consequence: PER1 NM_002616.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.489
• Publications: 2 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 17-8142640-G-A is Benign according to our data. Variant chr17-8142640-G-A is described in ClinVar as Benign. ClinVar VariationId is 771764.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3 gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PER1	NM_002616.3	MANE Select	c.3259+9C>T		intron	N/A	NP_002607.2	O15534-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PER1	ENST00000317276.9	TSL:1 MANE Select	c.3259+9C>T		intron	N/A	ENSP00000314420.4	O15534-1
	PER1	ENST00000857860.1		c.3259+9C>T		intron	N/A	ENSP00000527919.1
	PER1	ENST00000857861.1		c.3256+9C>T		intron	N/A	ENSP00000527920.1

Frequencies

GnomAD3 genomes AF: 0.00535 AC: 814 AN: 152220 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00150

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00641

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00574

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00842

Gnomad OTH AF: 0.00621

GnomAD2 exomes AF: 0.00564 AC: 1404 AN: 248796 AF XY: 0.00568

Gnomad AFR exome AF: 0.00123

Gnomad AMR exome AF: 0.00434

Gnomad ASJ exome AF: 0.00408

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00689

Gnomad NFE exome AF: 0.00895

Gnomad OTH exome AF: 0.00639

GnomAD4 exome AF: 0.00721 AC: 10528 AN: 1460756 Hom.: 45 Cov.: 34 AF XY: 0.00703 AC XY: 5108 AN XY: 726504

African (AFR) AF: 0.00120 AC: 40 AN: 33458

American (AMR) AF: 0.00439 AC: 196 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00306 AC: 80 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.000232 AC: 20 AN: 86238

European-Finnish (FIN) AF: 0.00730 AC: 388 AN: 53162

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5760

European-Non Finnish (NFE) AF: 0.00847 AC: 9410 AN: 1111314

Other (OTH) AF: 0.00640 AC: 386 AN: 60346

GnomAD4 genome AF: 0.00535 AC: 815 AN: 152338 Hom.: 3 Cov.: 32 AF XY: 0.00510 AC XY: 380 AN XY: 74484

African (AFR) AF: 0.00149 AC: 62 AN: 41582

American (AMR) AF: 0.00640 AC: 98 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00574 AC: 61 AN: 10618

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00842 AC: 573 AN: 68038

Other (OTH) AF: 0.00615 AC: 13 AN: 2114

Alfa AF: 0.00636 Hom.: 2

Bravo AF: 0.00493

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00845

EpiControl AF: 0.0106

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	3.6
DANN	Benign	0.94
PhyloP100		-0.49
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs146151077; hg19: chr17-8045958; COSMIC: COSV57920229;