rs2229101

Variant names:

• chr14-20377362-A-C
• rs2229101
• NM_007110.5:c.6006T>G

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.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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.271
• Publications: 9 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=-0.87).
• 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEP1	NM_007110.5	MANE Select	c.6006T>G	p.Leu2002Leu	synonymous	Exon 41 of 55	NP_009041.2
	TEP1	NM_001319035.2		c.5682T>G	p.Leu1894Leu	synonymous	Exon 39 of 53	NP_001305964.1	G3V5X7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEP1	ENST00000262715.10	TSL:1 MANE Select	c.6006T>G	p.Leu2002Leu	synonymous	Exon 41 of 55	ENSP00000262715.5	Q99973-1
	TEP1	ENST00000556935.5	TSL:1	c.5682T>G	p.Leu1894Leu	synonymous	Exon 39 of 53	ENSP00000452574.1	G3V5X7
	TEP1	ENST00000555008.5	TSL:1	n.4035T>G		non_coding_transcript_exon	Exon 29 of 43	ENSP00000450541.1	G3V2A4

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

GnomAD2 exomes AF: 0.0597 AC: 15006 AN: 251364 AF XY: 0.0628

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

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: 13 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

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

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: 7 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: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0611 AC: 4157 AN: 68014

Other (OTH) AF: 0.0629 AC: 133 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.80
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2229101; hg19: chr14-20845521;