rs2104977

Variant names:

• chr14-20370554-G-A
• rs2104977
• NM_007110.5:c.7317+664C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007110.5(TEP1):​c.7317+664C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,168 control chromosomes in the GnomAD database, including 1,361 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 0.12 (1361 hom., cov: 32)
• Consequence: TEP1 NM_007110.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91
• Publications: 7 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEP1	NM_007110.5	c.7317+664C>T		intron_variant	Intron 51 of 54	ENST00000262715.10	NP_009041.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEP1	ENST00000262715.10	c.7317+664C>T		intron_variant	Intron 51 of 54	1	NM_007110.5	ENSP00000262715.5

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18952 AN: 152050 Hom.: 1362 Cov.: 32

Gnomad AFR AF: 0.0516

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.124 AC: 18939 AN: 152168 Hom.: 1361 Cov.: 32 AF XY: 0.121 AC XY: 8994 AN XY: 74402

African (AFR) AF: 0.0515 AC: 2138 AN: 41520

American (AMR) AF: 0.121 AC: 1846 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 490 AN: 3468

East Asian (EAS) AF: 0.182 AC: 941 AN: 5180

South Asian (SAS) AF: 0.169 AC: 817 AN: 4826

European-Finnish (FIN) AF: 0.126 AC: 1332 AN: 10574

Middle Eastern (MID) AF: 0.0993 AC: 29 AN: 292

European-Non Finnish (NFE) AF: 0.161 AC: 10947 AN: 67996

Other (OTH) AF: 0.124 AC: 262 AN: 2114

Alfa AF: 0.154 Hom.: 2051

Bravo AF: 0.121

Asia WGS AF: 0.152 AC: 528 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.10
DANN	Benign	0.58
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2104977; hg19: chr14-20838713;