17-8143314-G-A

Variant names:

• chr17-8143314-G-A
• rs201554235
• NM_002616.3:c.3024C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_002616.3(PER1):​c.3024C>T​(p.Ala1008Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00188 in 1,595,170 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (37 hom.)
• Consequence: PER1 NM_002616.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.609
• Publications: 0 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 17-8143314-G-A is Benign according to our data. Variant chr17-8143314-G-A is described in ClinVar as Benign. ClinVar VariationId is 784353.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.609 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0014 (213/152220) while in subpopulation SAS AF = 0.0284 (137/4828). AF 95% confidence interval is 0.0245. There are 3 homozygotes in GnomAd4. There are 136 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• 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.3024C>T	p.Ala1008Ala	synonymous	Exon 19 of 23	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.3024C>T	p.Ala1008Ala	synonymous	Exon 19 of 23	ENSP00000314420.4	O15534-1
	PER1	ENST00000857860.1		c.3024C>T	p.Ala1008Ala	synonymous	Exon 19 of 23	ENSP00000527919.1
	PER1	ENST00000857861.1		c.3021C>T	p.Ala1007Ala	synonymous	Exon 19 of 23	ENSP00000527920.1

Frequencies

GnomAD3 genomes AF: 0.00139 AC: 211 AN: 152102 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00138

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.0281

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00420 AC: 973 AN: 231728 AF XY: 0.00530

Gnomad AFR exome AF: 0.00128

Gnomad AMR exome AF: 0.000120

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00254

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000871

Gnomad OTH exome AF: 0.00394

GnomAD4 exome AF: 0.00193 AC: 2785 AN: 1442950 Hom.: 37 Cov.: 31 AF XY: 0.00268 AC XY: 1919 AN XY: 715832

African (AFR) AF: 0.00139 AC: 46 AN: 33174

American (AMR) AF: 0.000138 AC: 6 AN: 43440

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24704

East Asian (EAS) AF: 0.00109 AC: 43 AN: 39428

South Asian (SAS) AF: 0.0289 AC: 2413 AN: 83538

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51970

Middle Eastern (MID) AF: 0.00132 AC: 7 AN: 5300

European-Non Finnish (NFE) AF: 0.0000753 AC: 83 AN: 1101872

Other (OTH) AF: 0.00314 AC: 187 AN: 59524

GnomAD4 genome AF: 0.00140 AC: 213 AN: 152220 Hom.: 3 Cov.: 32 AF XY: 0.00183 AC XY: 136 AN XY: 74424

African (AFR) AF: 0.00137 AC: 57 AN: 41526

American (AMR) AF: 0.000196 AC: 3 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5164

South Asian (SAS) AF: 0.0284 AC: 137 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 67998

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000474 Hom.: 0

Bravo AF: 0.000748

Asia WGS AF: 0.0310 AC: 107 AN: 3478

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	-0.53
CADD	Benign	6.5
DANN	Benign	0.78
PhyloP100		0.61
Mutation Taster		=100/0	polymorphism

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: rs201554235; hg19: chr17-8046632;