14-20413368-T-C

Position:

• chr14-20413368-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+37A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 152,146 control chromosomes in the GnomAD database, including 14,896 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 0.44 (14883 hom., cov: 32)
  • Exomes 𝑓: 0.49 (13 hom.)
• Consequence: TEP1 NM_007110.5 intron
• Scores: Splicing: ADA: 0.00002938
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.133

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEP1	NM_007110.5	c.-25+37A>G		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+37A>G		intron_variant		1	NM_007110.5	ENSP00000262715.5
TEP1	ENST00000556935.5	c.-25+37A>G		intron_variant		1		ENSP00000452574.1
TEP1	ENST00000555727.5	n.-25+37A>G		intron_variant		1		ENSP00000451634.1
TEP1	ENST00000556549.1	c.-25+3A>G		splice_region_variant, intron_variant		3		ENSP00000452240.1

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66647 AN: 151912 Hom.: 14856 Cov.: 32

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.459

GnomAD4 exome AF: 0.491 AC: 57 AN: 116 Hom.: 13 Cov.: 0 AF XY: 0.551 AC XY: 43 AN XY: 78

Gnomad4 AFR exome AF: 0.333

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.523

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.439 AC: 66713 AN: 152030 Hom.: 14883 Cov.: 32 AF XY: 0.430 AC XY: 31981 AN XY: 74314

Gnomad4 AFR AF: 0.470

Gnomad4 AMR AF: 0.505

Gnomad4 ASJ AF: 0.461

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.361

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.437

Gnomad4 OTH AF: 0.456

Alfa AF: 0.435 Hom.: 20734

Bravo AF: 0.458

Asia WGS AF: 0.361 AC: 1253 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.8
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000029
dbscSNV1_RF	Benign	0.0
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: rs1713434; hg19: chr14-20881527;