rs2184282

chr14-20412001-T-C

Variant summary

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

The NM_007110.5(TEP1):c.-25+1404A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,070 control chromosomes in the GnomAD database, including 1,459 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 0.13 (1459 hom., cov: 31)
• Consequence: TEP1 NM_007110.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.689

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TEP1	NM_007110.5	c.-25+1404A>G		intron_variant		ENST00000262715.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEP1	ENST00000262715.10	c.-25+1404A>G		intron_variant		1	NM_007110.5	P1
TEP1	ENST00000556935.5	c.-25+1404A>G		intron_variant		1
TEP1	ENST00000555727.5	c.-25+1404A>G		intron_variant, NMD_transcript_variant		1
TEP1	ENST00000556549.1	c.-25+1370A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20344 AN: 151950 Hom.: 1453 Cov.: 31

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.0963

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.134 AC: 20366 AN: 152070 Hom.: 1459 Cov.: 31 AF XY: 0.134 AC XY: 9945 AN XY: 74350

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.115

Gnomad4 ASJ AF: 0.0963

Gnomad4 EAS AF: 0.231

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.130

Alfa AF: 0.126 Hom.: 1706

Bravo AF: 0.132

Asia WGS AF: 0.186 AC: 648 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	5.1
Dann	Benign	0.81

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: rs2184282; hg19: chr14-20880160;