rs2229101

Positions:

• chr14-20377362-A-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_007110.5(TEP1):​c.6006T>G​(p.Leu2002=) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.271

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
TEP1	NM_007110.5	c.6006T>G	p.Leu2002=	synonymous_variant	41/55	ENST00000262715.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEP1	ENST00000262715.10	c.6006T>G	p.Leu2002=	synonymous_variant	41/55	1	NM_007110.5	P1

Frequencies

GnomAD3 genomes AF: 0.0649 AC: 9870 AN: 152156 Hom.: 374 Cov.: 32

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

GnomAD3 exomes AF: 0.0597 AC: 15006 AN: 251364 Hom.: 584 AF XY: 0.0628 AC XY: 8534 AN XY: 135874

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 SAS exome AF: 0.0946

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.: 33 AF XY: 0.0656 AC XY: 47737 AN XY: 727204

Gnomad4 AFR exome AF: 0.0827

Gnomad4 AMR exome AF: 0.0320

Gnomad4 ASJ exome AF: 0.0761

Gnomad4 EAS exome AF: 0.000327

Gnomad4 SAS exome AF: 0.0927

Gnomad4 FIN exome AF: 0.0679

Gnomad4 NFE exome AF: 0.0651

Gnomad4 OTH exome AF: 0.0613

GnomAD4 genome AF: 0.0649 AC: 9877 AN: 152274 Hom.: 375 Cov.: 32 AF XY: 0.0650 AC XY: 4842 AN XY: 74450

Gnomad4 AFR AF: 0.0833

Gnomad4 AMR AF: 0.0404

Gnomad4 ASJ AF: 0.0723

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0941

Gnomad4 FIN AF: 0.0707

Gnomad4 NFE AF: 0.0611

Gnomad4 OTH AF: 0.0629

Alfa AF: 0.0640 Hom.: 243

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
DANN	Benign	0.80

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

Other links and lift over

dbSNP: rs2229101; hg19: chr14-20845521;