14-20368557-C-T

Variant names:

• chr14-20368557-C-T
• rs8011960
• NM_007110.5:c.7764G>A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_007110.5(TEP1):​c.7764G>A​(p.Leu2588Leu) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00207 in 1,614,112 control chromosomes in the GnomAD database, including 70 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (37 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (33 hom.)
• Consequence: TEP1 NM_007110.5 splice_region, synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.72
• Publications: 0 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 -16 ACMG points.

• BP6: Variant 14-20368557-C-T is Benign according to our data. Variant chr14-20368557-C-T is described in ClinVar as Benign. ClinVar VariationId is 782579.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0112 (1705/152252) while in subpopulation AFR AF = 0.0392 (1626/41518). AF 95% confidence interval is 0.0376. There are 37 homozygotes in GnomAd4. There are 827 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1705 AD gene.

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.7764G>A	p.Leu2588Leu	splice_region synonymous	Exon 55 of 55	NP_009041.2
	TEP1	NM_001319035.2		c.7440G>A	p.Leu2480Leu	splice_region synonymous	Exon 53 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.7764G>A	p.Leu2588Leu	splice_region synonymous	Exon 55 of 55	ENSP00000262715.5	Q99973-1
	TEP1	ENST00000556935.5	TSL:1	c.7440G>A	p.Leu2480Leu	splice_region synonymous	Exon 53 of 53	ENSP00000452574.1	G3V5X7
	TEP1	ENST00000553365.5	TSL:1	n.*128G>A		splice_region non_coding_transcript_exon	Exon 8 of 9	ENSP00000450475.1	H0YIY9

Frequencies

GnomAD3 genomes AF: 0.0112 AC: 1704 AN: 152134 Hom.: 37 Cov.: 32

Gnomad AFR AF: 0.0393

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00353

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00908

GnomAD2 exomes AF: 0.00287 AC: 715 AN: 249050 AF XY: 0.00222

Gnomad AFR exome AF: 0.0380

Gnomad AMR exome AF: 0.00234

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000449

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00112 AC: 1630 AN: 1461860 Hom.: 33 Cov.: 31 AF XY: 0.000985 AC XY: 716 AN XY: 727218

African (AFR) AF: 0.0395 AC: 1322 AN: 33480

American (AMR) AF: 0.00271 AC: 121 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5768

European-Non Finnish (NFE) AF: 0.0000405 AC: 45 AN: 1111990

Other (OTH) AF: 0.00219 AC: 132 AN: 60394

GnomAD4 genome AF: 0.0112 AC: 1705 AN: 152252 Hom.: 37 Cov.: 32 AF XY: 0.0111 AC XY: 827 AN XY: 74436

African (AFR) AF: 0.0392 AC: 1626 AN: 41518

American (AMR) AF: 0.00353 AC: 54 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68032

Other (OTH) AF: 0.00899 AC: 19 AN: 2114

Alfa AF: 0.00537 Hom.: 11

Bravo AF: 0.0130

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	13
DANN	Benign	0.59
PhyloP100		1.7
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.26		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.26		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8011960; hg19: chr14-20836716;