rs872072

Positions:

• chr14-20390854-G-A
• chr14-20390854-G-C

Variant summary

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

The ENST00000262715.10(TEP1):​c.2256+84C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 1,611,362 control chromosomes in the GnomAD database, including 170,397 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 0.54 (24038 hom., cov: 32)
  • Exomes 𝑓: 0.44 (146359 hom.)
• Consequence: TEP1 ENST00000262715.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.288

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEP1	NM_007110.5	c.2256+84C>T		intron_variant		ENST00000262715.10	NP_009041.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEP1	ENST00000262715.10	c.2256+84C>T		intron_variant		1	NM_007110.5	ENSP00000262715	P1
TEP1	ENST00000556935.5	c.1932+84C>T		intron_variant		1		ENSP00000452574
TEP1	ENST00000555008.5	c.306+84C>T		intron_variant, NMD_transcript_variant		1		ENSP00000450541
TEP1	ENST00000555727.5	c.2256+84C>T		intron_variant, NMD_transcript_variant		1		ENSP00000451634

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81570 AN: 151934 Hom.: 23985 Cov.: 32

Gnomad AFR AF: 0.798

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.518

GnomAD4 exome AF: 0.442 AC: 644965 AN: 1459310 Hom.: 146359 Cov.: 35 AF XY: 0.441 AC XY: 319912 AN XY: 725708

Gnomad4 AFR exome AF: 0.812

Gnomad4 AMR exome AF: 0.441

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.237

Gnomad4 SAS exome AF: 0.433

Gnomad4 FIN exome AF: 0.447

Gnomad4 NFE exome AF: 0.436

Gnomad4 OTH exome AF: 0.459

GnomAD4 genome AF: 0.537 AC: 81682 AN: 152052 Hom.: 24038 Cov.: 32 AF XY: 0.536 AC XY: 39856 AN XY: 74304

Gnomad4 AFR AF: 0.798

Gnomad4 AMR AF: 0.472

Gnomad4 ASJ AF: 0.510

Gnomad4 EAS AF: 0.287

Gnomad4 SAS AF: 0.442

Gnomad4 FIN AF: 0.460

Gnomad4 NFE AF: 0.434

Gnomad4 OTH AF: 0.520

Alfa AF: 0.432 Hom.: 7552

Bravo AF: 0.548

Asia WGS AF: 0.391 AC: 1363 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.82
DANN	Benign	0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs872072; hg19: chr14-20859013;