rs2228026

chr14-20395890-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_007110.5(TEP1):c.1719T>C(p.Ile573=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0499 in 1,613,912 control chromosomes in the GnomAD database, including 2,297 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 0.038 (153 hom., cov: 32)
  • Exomes 𝑓: 0.051 (2144 hom.)
• Consequence: TEP1 NM_007110.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0740

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=-0.074 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TEP1	NM_007110.5	c.1719T>C	p.Ile573=	synonymous_variant	11/55	ENST00000262715.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEP1	ENST00000262715.10	c.1719T>C	p.Ile573=	synonymous_variant	11/55	1	NM_007110.5	P1
TEP1	ENST00000556935.5	c.1395T>C	p.Ile465=	synonymous_variant	9/53	1
TEP1	ENST00000555727.5	c.1719T>C	p.Ile573=	synonymous_variant, NMD_transcript_variant	11/54	1

Frequencies

GnomAD3 genomes AF: 0.0385 AC: 5856 AN: 152128 Hom.: 153 Cov.: 32

Gnomad AFR AF: 0.00946

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0321

Gnomad ASJ AF: 0.0655

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0878

Gnomad FIN AF: 0.0658

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0511

Gnomad OTH AF: 0.0435

GnomAD3 exomes AF: 0.0473 AC: 11898 AN: 251412 Hom.: 406 AF XY: 0.0517 AC XY: 7018 AN XY: 135876

Gnomad AFR exome AF: 0.00867

Gnomad AMR exome AF: 0.0227

Gnomad ASJ exome AF: 0.0658

Gnomad EAS exome AF: 0.000381

Gnomad SAS exome AF: 0.0899

Gnomad FIN exome AF: 0.0646

Gnomad NFE exome AF: 0.0514

Gnomad OTH exome AF: 0.0497

GnomAD4 exome AF: 0.0511 AC: 74626 AN: 1461666 Hom.: 2144 Cov.: 31 AF XY: 0.0528 AC XY: 38363 AN XY: 727146

Gnomad4 AFR exome AF: 0.00777

Gnomad4 AMR exome AF: 0.0243

Gnomad4 ASJ exome AF: 0.0676

Gnomad4 EAS exome AF: 0.000327

Gnomad4 SAS exome AF: 0.0883

Gnomad4 FIN exome AF: 0.0612

Gnomad4 NFE exome AF: 0.0514

Gnomad4 OTH exome AF: 0.0498

GnomAD4 genome AF: 0.0385 AC: 5855 AN: 152246 Hom.: 153 Cov.: 32 AF XY: 0.0403 AC XY: 3000 AN XY: 74444

Gnomad4 AFR AF: 0.00944

Gnomad4 AMR AF: 0.0321

Gnomad4 ASJ AF: 0.0655

Gnomad4 EAS AF: 0.000966

Gnomad4 SAS AF: 0.0875

Gnomad4 FIN AF: 0.0658

Gnomad4 NFE AF: 0.0511

Gnomad4 OTH AF: 0.0431

Alfa AF: 0.0464 Hom.: 83

Bravo AF: 0.0331

Asia WGS AF: 0.0300 AC: 104 AN: 3478

EpiCase AF: 0.0510

EpiControl AF: 0.0520

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.9
Dann	Benign	0.65

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: rs2228026; hg19: chr14-20864049;