Variant rs2104978 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_007110.5(TEP1):c.7685A>G(p.His2562Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0622 in 1,613,536 control chromosomes in the GnomAD database, including 3,450 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.045 ( 219 hom., cov: 32)

Exomes 𝑓: 0.064 ( 3231 hom. )

Consequence

TEP1
NM_007110.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.04

Variant links:

Genes affected

TEP1 (HGNC:11726): (telomerase associated protein 1) This gene product is a component of the ribonucleoprotein complex responsible for telomerase activity which catalyzes the addition of new telomeres on the chromosome ends. The telomerase-associated proteins are conserved from ciliates to humans. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

TEP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004953891).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.083 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TEP1	NM_007110.5 linkuse as main transcript	c.7685A>G	p.His2562Arg	missense_variant	54/55	ENST00000262715.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEP1	ENST00000262715.10 linkuse as main transcript	c.7685A>G	p.His2562Arg	missense_variant	54/55	1	NM_007110.5	P1	Q99973-1

Frequencies

GnomAD3 genomes

AF:

0.0449

AC:

6823

AN:

151976

Hom.:

219

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0119

Gnomad AMI

AF:

0.0242

Gnomad AMR

AF:

0.0334

Gnomad ASJ

AF:

0.0490

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0899

Gnomad FIN

AF:

0.0695

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0639

Gnomad OTH

AF:

0.0420

GnomAD3 exomes

AF:

0.0530

AC:

13305

AN:

250980

Hom.:

473

AF XY:

0.0572

AC XY:

7755

AN XY:

135636

show subpopulations

Gnomad AFR exome

AF:

0.0108

Gnomad AMR exome

AF:

0.0258

Gnomad ASJ exome

AF:

0.0522

Gnomad EAS exome

AF:

0.000598

Gnomad SAS exome

AF:

0.0899

Gnomad FIN exome

AF:

0.0701

Gnomad NFE exome

AF:

0.0628

Gnomad OTH exome

AF:

0.0516

GnomAD4 exome

AF:

0.0640

AC:

93499

AN:

1461442

Hom.:

3231

Cov.:

AF XY:

0.0650

AC XY:

47264

AN XY:

727010

show subpopulations

Gnomad4 AFR exome

AF:

0.00974

Gnomad4 AMR exome

AF:

0.0272

Gnomad4 ASJ exome

AF:

0.0532

Gnomad4 EAS exome

AF:

0.000327

Gnomad4 SAS exome

AF:

0.0886

Gnomad4 FIN exome

AF:

0.0677

Gnomad4 NFE exome

AF:

0.0678

Gnomad4 OTH exome

AF:

0.0578

GnomAD4 genome

AF:

0.0449

AC:

6823

AN:

152094

Hom.:

219

Cov.:

AF XY:

0.0460

AC XY:

3424

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.0119

Gnomad4 AMR

AF:

0.0334

Gnomad4 ASJ

AF:

0.0490

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.0900

Gnomad4 FIN

AF:

0.0695

Gnomad4 NFE

AF:

0.0639

Gnomad4 OTH

AF:

0.0416

Alfa

AF:

0.0580

Hom.:

586

Bravo

AF:

0.0397

TwinsUK

AF:

0.0723

AC:

268

ALSPAC

AF:

0.0664

AC:

256

ESP6500AA

AF:

0.0141

AC:

ESP6500EA

AF:

0.0663

AC:

570

ExAC

AF:

0.0536

AC:

6510

Asia WGS

AF:

0.0350

AC:

121

AN:

3476

EpiCase

AF:

0.0636

EpiControl

AF:

0.0613

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

T;T

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.76

T;T

MetaRNN

Benign

0.0050

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;.

MutationTaster

Benign

0.84

D;D

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-2.0

N;N

REVEL

Benign

0.21

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.55

MPC

0.59

ClinPred

0.017

GERP RS

5.8

Varity_R

0.31

gMVP

0.24

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over