14-20413368-T-C

Variant names:

• chr14-20413368-T-C
• rs1713434
• NM_007110.5:c.-25+37A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 24 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]

ENSG00000300624 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TEP1	NM_007110.5	c.-25+37A>G		intron_variant	Intron 1 of 54	ENST00000262715.10	NP_009041.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEP1	ENST00000262715.10	c.-25+37A>G		intron_variant	Intron 1 of 54	1	NM_007110.5	ENSP00000262715.5

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

African (AFR) AF: 0.333 AC: 2 AN: 6

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

South Asian (SAS) AF: 0.500 AC: 2 AN: 4

European-Finnish (FIN) AF: 0.500 AC: 4 AN: 8

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.523 AC: 45 AN: 86

Other (OTH) AF: 0.500 AC: 3 AN: 6

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

African (AFR) AF: 0.470 AC: 19484 AN: 41460

American (AMR) AF: 0.505 AC: 7710 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.461 AC: 1599 AN: 3472

East Asian (EAS) AF: 0.253 AC: 1304 AN: 5150

South Asian (SAS) AF: 0.361 AC: 1740 AN: 4820

European-Finnish (FIN) AF: 0.330 AC: 3496 AN: 10578

Middle Eastern (MID) AF: 0.438 AC: 128 AN: 292

European-Non Finnish (NFE) AF: 0.437 AC: 29666 AN: 67954

Other (OTH) AF: 0.456 AC: 965 AN: 2116

Alfa AF: 0.438 Hom.: 31418

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
PhyloP100		0.13
PromoterAI		-0.49	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1713434; hg19: chr14-20881527;