chr14-20368874-T-C

Variant names:

• chr14-20368874-T-C
• rs2104978
• NM_007110.5:c.7685A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007110.5(TEP1):​c.7685A>G​(p.His2562Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0622 in 1,613,536 control chromosomes in the GnomAD database, including 3,450 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 0.045 (219 hom., cov: 32)
  • Exomes 𝑓: 0.064 (3231 hom.)
• Consequence: TEP1 NM_007110.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.04
• Publications: 18 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004953891).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.083 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEP1	NM_007110.5	c.7685A>G	p.His2562Arg	missense_variant	Exon 54 of 55	ENST00000262715.10	NP_009041.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEP1	ENST00000262715.10	c.7685A>G	p.His2562Arg	missense_variant	Exon 54 of 55	1	NM_007110.5	ENSP00000262715.5

Frequencies

GnomAD3 genomes AF: 0.0449 AC: 6823 AN: 151976 Hom.: 219 Cov.: 32

Gnomad AFR AF: 0.0119

Gnomad AMI AF: 0.0242

Gnomad AMR AF: 0.0334

Gnomad ASJ AF: 0.0490

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0899

Gnomad FIN AF: 0.0695

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0639

Gnomad OTH AF: 0.0420

GnomAD2 exomes AF: 0.0530 AC: 13305 AN: 250980 AF XY: 0.0572

Gnomad AFR exome AF: 0.0108

Gnomad AMR exome AF: 0.0258

Gnomad ASJ exome AF: 0.0522

Gnomad EAS exome AF: 0.000598

Gnomad FIN exome AF: 0.0701

Gnomad NFE exome AF: 0.0628

Gnomad OTH exome AF: 0.0516

GnomAD4 exome AF: 0.0640 AC: 93499 AN: 1461442 Hom.: 3231 Cov.: 34 AF XY: 0.0650 AC XY: 47264 AN XY: 727010

African (AFR) AF: 0.00974 AC: 326 AN: 33476

American (AMR) AF: 0.0272 AC: 1215 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.0532 AC: 1391 AN: 26130

East Asian (EAS) AF: 0.000327 AC: 13 AN: 39696

South Asian (SAS) AF: 0.0886 AC: 7637 AN: 86196

European-Finnish (FIN) AF: 0.0677 AC: 3617 AN: 53392

Middle Eastern (MID) AF: 0.0675 AC: 389 AN: 5762

European-Non Finnish (NFE) AF: 0.0678 AC: 75420 AN: 1111720

Other (OTH) AF: 0.0578 AC: 3491 AN: 60376

GnomAD4 genome AF: 0.0449 AC: 6823 AN: 152094 Hom.: 219 Cov.: 32 AF XY: 0.0460 AC XY: 3424 AN XY: 74380

African (AFR) AF: 0.0119 AC: 494 AN: 41464

American (AMR) AF: 0.0334 AC: 511 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0490 AC: 170 AN: 3470

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5170

South Asian (SAS) AF: 0.0900 AC: 434 AN: 4822

European-Finnish (FIN) AF: 0.0695 AC: 735 AN: 10576

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

European-Non Finnish (NFE) AF: 0.0639 AC: 4341 AN: 67986

Other (OTH) AF: 0.0416 AC: 88 AN: 2116

Alfa AF: 0.0561 Hom.: 1153

Bravo AF: 0.0397

TwinsUK AF: 0.0723 AC: 268

ALSPAC AF: 0.0664 AC: 256

ESP6500AA AF: 0.0141 AC: 62

ESP6500EA AF: 0.0663 AC: 570

ExAC AF: 0.0536 AC: 6510

Asia WGS AF: 0.0350 AC: 121 AN: 3476

EpiCase AF: 0.0636

EpiControl AF: 0.0613

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.76	T;T
MetaRNN	Benign	0.0050	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;.
PhyloP100		4.0
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.55
MPC		0.59
ClinPred		0.017	T
GERP RS		5.8
Varity_R		0.31
gMVP		0.24
Mutation Taster		=95/5	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: rs2104978; hg19: chr14-20837033;