chr17-8152405-A-G

Variant names:

• chr17-8152405-A-G
• rs3027172
• ENST00000498285.1:c.335-1560T>C

Variant summary

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

The ENST00000498285.1(ENSG00000263620):​c.335-1560T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,514 control chromosomes in the GnomAD database, including 2,498 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 0.17 (2494 hom., cov: 33)
  • Exomes 𝑓: 0.17 (4 hom.)
• Consequence: ENSG00000263620 ENST00000498285.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.85
• Publications: 21 publications found

Genes affected

ENSG00000263620 (HGNC:):

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=0.0013884604).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000498285.1. 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.-208T>C		upstream_gene	N/A	NP_002607.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000263620	ENST00000498285.1	TSL:4	c.335-1560T>C		intron	N/A	ENSP00000464383.1
	PER1	ENST00000581703.1	TSL:4	c.28T>C	p.Trp10Arg	missense	Exon 1 of 4	ENSP00000463385.1
	PER1	ENST00000354903.9	TSL:2	c.49-1795T>C		intron	N/A	ENSP00000346979.5

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25504 AN: 152098 Hom.: 2494 Cov.: 33

Gnomad AFR AF: 0.0922

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.0378

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.162

GnomAD2 exomes AF: 0.382 AC: 71 AN: 186 AF XY: 0.412

Gnomad NFE exome AF: 0.385

Gnomad OTH exome AF: 0.250

GnomAD4 exome AF: 0.168 AC: 50 AN: 298 Hom.: 4 Cov.: 0 AF XY: 0.188 AC XY: 26 AN XY: 138

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 2 AN: 8

East Asian (EAS) AF: 0.00 AC: 0 AN: 44

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.269 AC: 7 AN: 26

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.191 AC: 36 AN: 188

Other (OTH) AF: 0.167 AC: 4 AN: 24

GnomAD4 genome AF: 0.168 AC: 25514 AN: 152216 Hom.: 2494 Cov.: 33 AF XY: 0.162 AC XY: 12085 AN XY: 74426

African (AFR) AF: 0.0922 AC: 3830 AN: 41542

American (AMR) AF: 0.147 AC: 2247 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 765 AN: 3468

East Asian (EAS) AF: 0.0375 AC: 194 AN: 5172

South Asian (SAS) AF: 0.116 AC: 560 AN: 4822

European-Finnish (FIN) AF: 0.153 AC: 1623 AN: 10620

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.231 AC: 15719 AN: 67974

Other (OTH) AF: 0.160 AC: 338 AN: 2114

Alfa AF: 0.192 Hom.: 380

Bravo AF: 0.165

TwinsUK AF: 0.246 AC: 914

ALSPAC AF: 0.234 AC: 903

ExAC AF: 0.0227 AC: 61

Asia WGS AF: 0.0710 AC: 246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	19
DANN	Benign	0.88
DEOGEN2	Benign	0.0084	T
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.12	T
MetaRNN	Benign	0.0014	T
PhyloP100		1.9
Sift4G	Benign	0.37	T
GERP RS		2.7
PromoterAI		0.072	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Mutation Taster		=300/0	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: rs3027172; hg19: chr17-8055723;