Genetic Variant NM_007110.5:c.6006T>G (chr14-20377362-A-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_007110.5(TEP1):c.6006T>G(p.Leu2002Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0646 in 1,614,060 control chromosomes in the GnomAD database, including 3,636 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 0.065 ( 375 hom., cov: 32)

Exomes 𝑓: 0.065 ( 3261 hom. )

Consequence

TEP1
NM_007110.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.271

Publications

9 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP7

Synonymous conserved (PhyloP=-0.271 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.087 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEP1	NM_007110.5 link	c.6006T>G	p.Leu2002Leu	synonymous_variant	Exon 41 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.6006T>G	p.Leu2002Leu	synonymous_variant	Exon 41 of 55	1	NM_007110.5	ENSP00000262715.5		Q99973-1

Frequencies

GnomAD3 genomes

AF:

0.0649

AC:

9870

AN:

152156

Hom.:

374

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0833

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.0404

Gnomad ASJ

AF:

0.0723

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0945

Gnomad FIN

AF:

0.0707

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0611

Gnomad OTH

AF:

0.0636

GnomAD2 exomes

AF:

0.0597

AC:

15006

AN:

251364

AF XY:

0.0628

show subpopulations

Gnomad AFR exome

AF:

0.0850

Gnomad AMR exome

AF:

0.0303

Gnomad ASJ exome

AF:

0.0761

Gnomad EAS exome

AF:

0.000598

Gnomad FIN exome

AF:

0.0708

Gnomad NFE exome

AF:

0.0617

Gnomad OTH exome

AF:

0.0575

GnomAD4 exome

AF:

0.0645

AC:

94329

AN:

1461786

Hom.:

3261

Cov.:

AF XY:

0.0656

AC XY:

47737

AN XY:

727204

show subpopulations

African (AFR)

AF:

0.0827

AC:

2770

AN:

33476

American (AMR)

AF:

0.0320

AC:

1429

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0761

AC:

1989

AN:

26132

East Asian (EAS)

AF:

0.000327

AC:

AN:

39700

South Asian (SAS)

AF:

0.0927

AC:

7997

AN:

86256

European-Finnish (FIN)

AF:

0.0679

AC:

3624

AN:

53410

Middle Eastern (MID)

AF:

0.0744

AC:

429

AN:

5768

European-Non Finnish (NFE)

AF:

0.0651

AC:

72373

AN:

1111930

Other (OTH)

AF:

0.0613

AC:

3705

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

4699

9398

14096

18795

23494

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2774

5548

8322

11096

13870

<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:

0.0649

AC:

9877

AN:

152274

Hom.:

375

Cov.:

AF XY:

0.0650

AC XY:

4842

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.0833

AC:

3460

AN:

41534

American (AMR)

AF:

0.0404

AC:

618

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0723

AC:

251

AN:

3470

East Asian (EAS)

AF:

0.00135

AC:

AN:

5182

South Asian (SAS)

AF:

0.0941

AC:

455

AN:

4834

European-Finnish (FIN)

AF:

0.0707

AC:

751

AN:

10620

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0611

AC:

4157

AN:

68014

Other (OTH)

AF:

0.0629

AC:

133

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

480

960

1441

1921

2401

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

118

236

354

472

590

<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:

0.0634

Hom.:

263

Bravo

AF:

0.0616

Asia WGS

AF:

0.0380

AC:

132

AN:

3474

EpiCase

AF:

0.0632

EpiControl

AF:

0.0627

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.3

(source)

DANN

Benign

0.80

PhyloP100

-0.27

Mutation Taster

=100/0

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