Genetic Variant NM_007110.5:c.7685A>G (chr14-20368874-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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.

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

Publications

18 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TEP1	NM_007110.5 link	c.7685A>G	p.His2562Arg	missense_variant	Exon 54 of 55	ENST00000262715.10	NP_009041.2	Q99973-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEP1	ENST00000262715.10 link	c.7685A>G	p.His2562Arg	missense_variant	Exon 54 of 55	1	NM_007110.5	ENSP00000262715.5		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

GnomAD2 exomes

AF:

0.0530

AC:

13305

AN:

250980

AF XY:

0.0572

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 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

African (AFR)

AF:

0.00974

AC:

326

AN:

33476

American (AMR)

AF:

0.0272

AC:

1215

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.0532

AC:

1391

AN:

26130

East Asian (EAS)

AF:

0.000327

AC:

AN:

39696

South Asian (SAS)

AF:

0.0886

AC:

7637

AN:

86196

European-Finnish (FIN)

AF:

0.0677

AC:

3617

AN:

53392

Middle Eastern (MID)

AF:

0.0675

AC:

389

AN:

5762

European-Non Finnish (NFE)

AF:

0.0678

AC:

75420

AN:

1111720

Other (OTH)

AF:

0.0578

AC:

3491

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

4232

8464

12696

16928

21160

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2826

5652

8478

11304

14130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0449

AC:

6823

AN:

152094

Hom.:

219

Cov.:

AF XY:

0.0460

AC XY:

3424

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.0119

AC:

494

AN:

41464

American (AMR)

AF:

0.0334

AC:

511

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0490

AC:

170

AN:

3470

East Asian (EAS)

AF:

0.00135

AC:

AN:

5170

South Asian (SAS)

AF:

0.0900

AC:

434

AN:

4822

European-Finnish (FIN)

AF:

0.0695

AC:

735

AN:

10576

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0639

AC:

4341

AN:

67986

Other (OTH)

AF:

0.0416

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

335

670

1006

1341

1676

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

184

276

368

460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0561

Hom.:

1153

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

(source)

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;.

PhyloP100

4.0

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

Mutation Taster

=95/5

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over