14-20376224-C-T

Variant names:

• chr14-20376224-C-T
• rs2228042
• NM_007110.5:c.6129G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_007110.5(TEP1):​c.6129G>A​(p.Thr2043Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0611 in 1,614,100 control chromosomes in the GnomAD database, including 3,336 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 0.046 (227 hom., cov: 32)
  • Exomes 𝑓: 0.063 (3109 hom.)
• Consequence: TEP1 NM_007110.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.39
• Publications: 10 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP7: Synonymous conserved (PhyloP=-4.39 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0878 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007110.5. 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.6129G>A	p.Thr2043Thr	synonymous	Exon 42 of 55	NP_009041.2
	TEP1	NM_001319035.2		c.5805G>A	p.Thr1935Thr	synonymous	Exon 40 of 53	NP_001305964.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEP1	ENST00000262715.10	TSL:1 MANE Select	c.6129G>A	p.Thr2043Thr	synonymous	Exon 42 of 55	ENSP00000262715.5
	TEP1	ENST00000556935.5	TSL:1	c.5805G>A	p.Thr1935Thr	synonymous	Exon 40 of 53	ENSP00000452574.1
	TEP1	ENST00000555008.5	TSL:1	n.4158G>A		non_coding_transcript_exon	Exon 30 of 43	ENSP00000450541.1

Frequencies

GnomAD3 genomes AF: 0.0462 AC: 7034 AN: 152148 Hom.: 227 Cov.: 32

Gnomad AFR AF: 0.0180

Gnomad AMI AF: 0.0264

Gnomad AMR AF: 0.0359

Gnomad ASJ AF: 0.0723

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0951

Gnomad FIN AF: 0.0686

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0610

Gnomad OTH AF: 0.0494

GnomAD2 exomes AF: 0.0547 AC: 13742 AN: 251154 AF XY: 0.0591

Gnomad AFR exome AF: 0.0182

Gnomad AMR exome AF: 0.0278

Gnomad ASJ exome AF: 0.0764

Gnomad EAS exome AF: 0.000598

Gnomad FIN exome AF: 0.0687

Gnomad NFE exome AF: 0.0614

Gnomad OTH exome AF: 0.0552

GnomAD4 exome AF: 0.0626 AC: 91537 AN: 1461834 Hom.: 3109 Cov.: 32 AF XY: 0.0640 AC XY: 46530 AN XY: 727224

African (AFR) AF: 0.0169 AC: 567 AN: 33480

American (AMR) AF: 0.0291 AC: 1301 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0761 AC: 1989 AN: 26130

East Asian (EAS) AF: 0.000327 AC: 13 AN: 39700

South Asian (SAS) AF: 0.0930 AC: 8023 AN: 86254

European-Finnish (FIN) AF: 0.0663 AC: 3539 AN: 53412

Middle Eastern (MID) AF: 0.0733 AC: 423 AN: 5768

European-Non Finnish (NFE) AF: 0.0649 AC: 72219 AN: 1111976

Other (OTH) AF: 0.0573 AC: 3463 AN: 60396

GnomAD4 genome AF: 0.0462 AC: 7035 AN: 152266 Hom.: 227 Cov.: 32 AF XY: 0.0471 AC XY: 3509 AN XY: 74448

African (AFR) AF: 0.0180 AC: 750 AN: 41562

American (AMR) AF: 0.0358 AC: 548 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0723 AC: 251 AN: 3472

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5184

South Asian (SAS) AF: 0.0950 AC: 458 AN: 4822

European-Finnish (FIN) AF: 0.0686 AC: 727 AN: 10590

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0610 AC: 4146 AN: 68020

Other (OTH) AF: 0.0489 AC: 103 AN: 2108

Alfa AF: 0.0548 Hom.: 280

Bravo AF: 0.0416

Asia WGS AF: 0.0350 AC: 122 AN: 3478

EpiCase AF: 0.0632

EpiControl AF: 0.0626

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.44
DANN	Benign	0.58
PhyloP100		-4.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2228042; hg19: chr14-20844383;