14-20382104-G-A

Position:

• chr14-20382104-G-A

Variant summary

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

The NM_007110.5(TEP1):​c.4274-41C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0463 in 1,611,580 control chromosomes in the GnomAD database, including 4,305 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 0.096 (1305 hom., cov: 32)
  • Exomes 𝑓: 0.041 (3000 hom.)
• Consequence: TEP1 NM_007110.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TEP1	NM_007110.5	c.4274-41C>T		intron_variant		ENST00000262715.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEP1	ENST00000262715.10	c.4274-41C>T		intron_variant		1	NM_007110.5	P1

Frequencies

GnomAD3 genomes AF: 0.0963 AC: 14624 AN: 151890 Hom.: 1299 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.0699

Gnomad FIN AF: 0.0261

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0247

Gnomad OTH AF: 0.0938

GnomAD3 exomes AF: 0.0789 AC: 19455 AN: 246490 Hom.: 1564 AF XY: 0.0704 AC XY: 9383 AN XY: 133234

Gnomad AFR exome AF: 0.216

Gnomad AMR exome AF: 0.210

Gnomad ASJ exome AF: 0.0177

Gnomad EAS exome AF: 0.166

Gnomad SAS exome AF: 0.0687

Gnomad FIN exome AF: 0.0237

Gnomad NFE exome AF: 0.0242

Gnomad OTH exome AF: 0.0639

GnomAD4 exome AF: 0.0411 AC: 60006 AN: 1459572 Hom.: 3000 Cov.: 34 AF XY: 0.0405 AC XY: 29424 AN XY: 725988

Gnomad4 AFR exome AF: 0.216

Gnomad4 AMR exome AF: 0.208

Gnomad4 ASJ exome AF: 0.0187

Gnomad4 EAS exome AF: 0.143

Gnomad4 SAS exome AF: 0.0685

Gnomad4 FIN exome AF: 0.0224

Gnomad4 NFE exome AF: 0.0240

Gnomad4 OTH exome AF: 0.0538

GnomAD4 genome AF: 0.0964 AC: 14658 AN: 152008 Hom.: 1305 Cov.: 32 AF XY: 0.0998 AC XY: 7417 AN XY: 74336

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.0153

Gnomad4 EAS AF: 0.168

Gnomad4 SAS AF: 0.0708

Gnomad4 FIN AF: 0.0261

Gnomad4 NFE AF: 0.0247

Gnomad4 OTH AF: 0.0923

Alfa AF: 0.0428 Hom.: 140

Bravo AF: 0.113

Asia WGS AF: 0.112 AC: 390 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.85
DANN	Benign	0.24
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs11850456; hg19: chr14-20850263; COSMIC: COSV53002657; COSMIC: COSV53002657;