Genetic Variant TEP1:c.-25+37A>G (chr14-20413368-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 ENST00000262715.10(TEP1):c.-25+37A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 152,146 control chromosomes in the GnomAD database, including 14,896 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 0.44 ( 14883 hom., cov: 32)

Exomes 𝑓: 0.49 ( 13 hom. )

Consequence

TEP1
ENST00000262715.10 intron

Scores

Splicing: ADA: 0.00002938

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.133

Publications

24 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:

ENSG00000300624 (HGNC:):

ENSG00000300624 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 (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000262715.10. 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
	TEP1	NM_007110.5	MANE Select	c.-25+37A>G		intron	N/A	NP_009041.2
	TEP1	NM_001319035.2		c.-25+37A>G		intron	N/A	NP_001305964.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TEP1	ENST00000262715.10	TSL:1 MANE Select	c.-25+37A>G	intron	N/A	ENSP00000262715.5
TEP1	ENST00000556935.5	TSL:1	c.-25+37A>G	intron	N/A	ENSP00000452574.1
TEP1	ENST00000555727.5	TSL:1	n.-25+37A>G	intron	N/A	ENSP00000451634.1

Frequencies

GnomAD3 genomes

AF:

0.439

AC:

66647

AN:

151912

Hom.:

14856

Cov.:

show subpopulations

Gnomad AFR

AF:

0.470

Gnomad AMI

AF:

0.682

Gnomad AMR

AF:

0.504

Gnomad ASJ

AF:

0.461

Gnomad EAS

AF:

0.253

Gnomad SAS

AF:

0.360

Gnomad FIN

AF:

0.330

Gnomad MID

AF:

0.420

Gnomad NFE

AF:

0.437

Gnomad OTH

AF:

0.459

GnomAD4 exome

AF:

0.491

AC:

AN:

116

Hom.:

Cov.:

AF XY:

0.551

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.333

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.523

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.439

AC:

66713

AN:

152030

Hom.:

14883

Cov.:

AF XY:

0.430

AC XY:

31981

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.470

AC:

19484

AN:

41460

American (AMR)

AF:

0.505

AC:

7710

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.461

AC:

1599

AN:

3472

East Asian (EAS)

AF:

0.253

AC:

1304

AN:

5150

South Asian (SAS)

AF:

0.361

AC:

1740

AN:

4820

European-Finnish (FIN)

AF:

0.330

AC:

3496

AN:

10578

Middle Eastern (MID)

AF:

0.438

AC:

128

AN:

292

European-Non Finnish (NFE)

AF:

0.437

AC:

29666

AN:

67954

Other (OTH)

AF:

0.456

AC:

965

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1968

3937

5905

7874

9842

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

610

1220

1830

2440

3050

<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:

0.438

Hom.:

31418

Bravo

AF:

0.458

Asia WGS

AF:

0.361

AC:

1253

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.8

(source)

DANN

Benign

0.59

PhyloP100

0.13

PromoterAI

-0.49

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000029

dbscSNV1_RF

Benign

0.0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over