rs2228026

Variant names:

• chr14-20395890-A-G
• rs2228026
• NM_007110.5:c.1719T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_007110.5(TEP1):​c.1719T>C​(p.Ile573Ile) 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
• Publications: 10 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]

TEP1 Gene-Disease associations (from GenCC):

• cerebral palsy

  Inheritance: AD Classification: MODERATE Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007110.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEP1	NM_007110.5	MANE Select	c.1719T>C	p.Ile573Ile	synonymous	Exon 11 of 55	NP_009041.2
	TEP1	NM_001319035.2		c.1395T>C	p.Ile465Ile	synonymous	Exon 9 of 53	NP_001305964.1	G3V5X7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEP1	ENST00000262715.10	TSL:1 MANE Select	c.1719T>C	p.Ile573Ile	synonymous	Exon 11 of 55	ENSP00000262715.5	Q99973-1
	TEP1	ENST00000556935.5	TSL:1	c.1395T>C	p.Ile465Ile	synonymous	Exon 9 of 53	ENSP00000452574.1	G3V5X7
	TEP1	ENST00000555727.5	TSL:1	n.1719T>C		non_coding_transcript_exon	Exon 11 of 54	ENSP00000451634.1	G3V470

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

GnomAD2 exomes AF: 0.0473 AC: 11898 AN: 251412 AF XY: 0.0517

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 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

African (AFR) AF: 0.00777 AC: 260 AN: 33478

American (AMR) AF: 0.0243 AC: 1086 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0676 AC: 1765 AN: 26126

East Asian (EAS) AF: 0.000327 AC: 13 AN: 39700

South Asian (SAS) AF: 0.0883 AC: 7613 AN: 86218

European-Finnish (FIN) AF: 0.0612 AC: 3270 AN: 53408

Middle Eastern (MID) AF: 0.0742 AC: 428 AN: 5766

European-Non Finnish (NFE) AF: 0.0514 AC: 57186 AN: 1111874

Other (OTH) AF: 0.0498 AC: 3005 AN: 60378

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

African (AFR) AF: 0.00944 AC: 392 AN: 41542

American (AMR) AF: 0.0321 AC: 491 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0655 AC: 227 AN: 3468

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5178

South Asian (SAS) AF: 0.0875 AC: 422 AN: 4824

European-Finnish (FIN) AF: 0.0658 AC: 698 AN: 10602

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0511 AC: 3476 AN: 68016

Other (OTH) AF: 0.0431 AC: 91 AN: 2112

Alfa AF: 0.0461 Hom.: 112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.9
DANN	Benign	0.65
PhyloP100		-0.074
Mutation Taster		=100/0	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: rs2228026; hg19: chr14-20864049;