14-20411152-T-G

Position:

• chr14-20411152-T-G

Variant summary

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

The ENST00000262715.10(TEP1):​c.-25+2253A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 151,936 control chromosomes in the GnomAD database, including 22,257 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 (22257 hom., cov: 31)
• Consequence: TEP1 ENST00000262715.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.557

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEP1	NM_007110.5	c.-25+2253A>C		intron_variant		ENST00000262715.10	NP_009041.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEP1	ENST00000262715.10	c.-25+2253A>C		intron_variant		1	NM_007110.5	ENSP00000262715	P1
TEP1	ENST00000556935.5	c.-25+2253A>C		intron_variant		1		ENSP00000452574
TEP1	ENST00000555727.5	c.-25+2253A>C		intron_variant, NMD_transcript_variant		1		ENSP00000451634
TEP1	ENST00000556549.1	c.-25+2219A>C		intron_variant		3		ENSP00000452240

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81736 AN: 151818 Hom.: 22237 Cov.: 31

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.594

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.541

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.538 AC: 81789 AN: 151936 Hom.: 22257 Cov.: 31 AF XY: 0.536 AC XY: 39832 AN XY: 74254

Gnomad4 AFR AF: 0.614

Gnomad4 AMR AF: 0.514

Gnomad4 ASJ AF: 0.524

Gnomad4 EAS AF: 0.594

Gnomad4 SAS AF: 0.403

Gnomad4 FIN AF: 0.547

Gnomad4 NFE AF: 0.503

Gnomad4 OTH AF: 0.538

Alfa AF: 0.515 Hom.: 21996

Bravo AF: 0.546

Asia WGS AF: 0.505 AC: 1760 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.6
DANN	Benign	0.69

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: rs2678685; hg19: chr14-20879311;