rs2297615

Positions:

• chr14-20378362-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007110.5(TEP1):​c.5508+18T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 1,613,754 control chromosomes in the GnomAD database, including 54,994 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 0.27 (5520 hom., cov: 32)
  • Exomes 𝑓: 0.26 (49474 hom.)
• Consequence: TEP1 NM_007110.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.65

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEP1	NM_007110.5	c.5508+18T>A		intron_variant		ENST00000262715.10	NP_009041.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEP1	ENST00000262715.10	c.5508+18T>A		intron_variant		1	NM_007110.5	ENSP00000262715.5

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40515 AN: 151972 Hom.: 5519 Cov.: 32

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.252

GnomAD3 exomes AF: 0.251 AC: 62984 AN: 251030 Hom.: 8207 AF XY: 0.252 AC XY: 34205 AN XY: 135690

Gnomad AFR exome AF: 0.328

Gnomad AMR exome AF: 0.197

Gnomad ASJ exome AF: 0.266

Gnomad EAS exome AF: 0.224

Gnomad SAS exome AF: 0.285

Gnomad FIN exome AF: 0.237

Gnomad NFE exome AF: 0.253

Gnomad OTH exome AF: 0.248

GnomAD4 exome AF: 0.258 AC: 377714 AN: 1461664 Hom.: 49474 Cov.: 36 AF XY: 0.260 AC XY: 188752 AN XY: 727122

Gnomad4 AFR exome AF: 0.330

Gnomad4 AMR exome AF: 0.197

Gnomad4 ASJ exome AF: 0.260

Gnomad4 EAS exome AF: 0.225

Gnomad4 SAS exome AF: 0.289

Gnomad4 FIN exome AF: 0.241

Gnomad4 NFE exome AF: 0.259

Gnomad4 OTH exome AF: 0.257

GnomAD4 genome AF: 0.267 AC: 40532 AN: 152090 Hom.: 5520 Cov.: 32 AF XY: 0.262 AC XY: 19450 AN XY: 74354

Gnomad4 AFR AF: 0.328

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.260

Gnomad4 EAS AF: 0.223

Gnomad4 SAS AF: 0.284

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.254

Gnomad4 OTH AF: 0.250

Alfa AF: 0.263 Hom.: 984

Bravo AF: 0.266

Asia WGS AF: 0.227 AC: 789 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.013
DANN	Benign	0.22

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: rs2297615; hg19: chr14-20846521; COSMIC: COSV52989727; COSMIC: COSV52989727;