Variant 15-64816596-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001286496.2(PIF1):c.1844G>A(p.Arg615Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00281 in 1,613,678 control chromosomes in the GnomAD database, including 141 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 63 hom., cov: 33)

Exomes 𝑓: 0.0016 ( 78 hom. )

Consequence

PIF1
NM_001286496.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.194

Variant links:

Genes affected

PIF1 (HGNC:26220): (PIF1 5'-to-3' DNA helicase) This gene encodes a DNA-dependent adenosine triphosphate (ATP)-metabolizing enzyme that functions as a 5' to 3' DNA helicase. The encoded protein can resolve G-quadruplex structures and RNA-DNA hybrids at the ends of chromosomes. It also prevents telomere elongation by inhibiting the actions of telomerase. Alternative splicing and the use of alternative start codons results in multiple isoforms that are differentially localized to either the mitochondria or the nucleus. [provided by RefSeq, Nov 2013]

PIF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023785532).

BP6

Variant 15-64816596-C-T is Benign according to our data. Variant chr15-64816596-C-T is described in ClinVar as [Benign]. Clinvar id is 787119.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIF1	NM_001286496.2 linkuse as main transcript	c.1844G>A	p.Arg615Gln	missense_variant	12/13	ENST00000559239.2	NP_001273425.1	Q9H611-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PIF1	ENST00000559239.2 linkuse as main transcript	c.1844G>A	p.Arg615Gln	missense_variant	12/13	1	NM_001286496.2	ENSP00000452792.1	Q9H611-1
PIF1	ENST00000333425.10 linkuse as main transcript	c.1844G>A	p.Arg615Gln	missense_variant	12/13	1		ENSP00000328174.6	Q9H611-3
PIF1	ENST00000268043.8 linkuse as main transcript	c.1844G>A	p.Arg615Gln	missense_variant	12/13	1		ENSP00000268043.4	Q9H611-1

Frequencies

GnomAD3 genomes

AF:

0.0148

AC:

2249

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0525

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00375

AC:

938

AN:

249846

Hom.:

AF XY:

0.00280

AC XY:

379

AN XY:

135378

show subpopulations

Gnomad AFR exome

AF:

0.0532

Gnomad AMR exome

AF:

0.00178

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000981

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000133

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00156

AC:

2283

AN:

1461346

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

982

AN XY:

727030

show subpopulations

Gnomad4 AFR exome

AF:

0.0576

Gnomad4 AMR exome

AF:

0.00211

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000603

Gnomad4 OTH exome

AF:

0.00287

GnomAD4 genome

AF:

0.0148

AC:

2259

AN:

152332

Hom.:

Cov.:

AF XY:

0.0142

AC XY:

1059

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0526

Gnomad4 AMR

AF:

0.00327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00260

Hom.:

Bravo

AF:

0.0163

ESP6500AA

AF:

0.0486

AC:

214

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00467

AC:

567

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.46

CADD

Benign

6.7

DANN

Benign

0.97

DEOGEN2

Benign

0.15

T;.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.65

.;T;T

MetaRNN

Benign

0.0024

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;L;L

PrimateAI

Benign

0.21

PROVEAN

Uncertain

-2.5

D;D;D

REVEL

Benign

0.099

Sift

Benign

0.10

T;T;T

Sift4G

Benign

0.088

T;T;T

Polyphen

0.051

B;.;B

Vest4

0.20

MVP

0.26

MPC

0.081

ClinPred

0.023

GERP RS

-4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.16

gMVP

0.26

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over