rs2297615

Variant names:

• chr14-20378362-A-T
• rs2297615
• NM_007110.5:c.5508+18T>A

Variant summary

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

The NM_007110.5(TEP1):​c.5508+18T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 1,613,754 control chromosomes in the GnomAD database, including 54,994 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 0.27 (5520 hom., cov: 32)
  • Exomes 𝑓: 0.26 (49474 hom.)
• Consequence: TEP1 NM_007110.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.65
• Publications: 10 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007110.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEP1	NM_007110.5	MANE Select	c.5508+18T>A		intron	N/A	NP_009041.2
	TEP1	NM_001319035.2		c.5184+18T>A		intron	N/A	NP_001305964.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEP1	ENST00000262715.10	TSL:1 MANE Select	c.5508+18T>A		intron	N/A	ENSP00000262715.5
	TEP1	ENST00000556935.5	TSL:1	c.5184+18T>A		intron	N/A	ENSP00000452574.1
	TEP1	ENST00000555008.5	TSL:1	n.3537+18T>A		intron	N/A	ENSP00000450541.1

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40515 AN: 151972 Hom.: 5519 Cov.: 32

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.252

GnomAD2 exomes AF: 0.251 AC: 62984 AN: 251030 AF XY: 0.252

Gnomad AFR exome AF: 0.328

Gnomad AMR exome AF: 0.197

Gnomad ASJ exome AF: 0.266

Gnomad EAS exome AF: 0.224

Gnomad FIN exome AF: 0.237

Gnomad NFE exome AF: 0.253

Gnomad OTH exome AF: 0.248

GnomAD4 exome AF: 0.258 AC: 377714 AN: 1461664 Hom.: 49474 Cov.: 36 AF XY: 0.260 AC XY: 188752 AN XY: 727122

African (AFR) AF: 0.330 AC: 11053 AN: 33478

American (AMR) AF: 0.197 AC: 8828 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 6802 AN: 26126

East Asian (EAS) AF: 0.225 AC: 8916 AN: 39696

South Asian (SAS) AF: 0.289 AC: 24967 AN: 86250

European-Finnish (FIN) AF: 0.241 AC: 12879 AN: 53404

Middle Eastern (MID) AF: 0.235 AC: 1357 AN: 5766

European-Non Finnish (NFE) AF: 0.259 AC: 287423 AN: 1111848

Other (OTH) AF: 0.257 AC: 15489 AN: 60384

GnomAD4 genome AF: 0.267 AC: 40532 AN: 152090 Hom.: 5520 Cov.: 32 AF XY: 0.262 AC XY: 19450 AN XY: 74354

African (AFR) AF: 0.328 AC: 13584 AN: 41462

American (AMR) AF: 0.200 AC: 3065 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 902 AN: 3472

East Asian (EAS) AF: 0.223 AC: 1153 AN: 5172

South Asian (SAS) AF: 0.284 AC: 1368 AN: 4822

European-Finnish (FIN) AF: 0.228 AC: 2420 AN: 10606

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.254 AC: 17271 AN: 67944

Other (OTH) AF: 0.250 AC: 529 AN: 2114

Alfa AF: 0.263 Hom.: 984

Bravo AF: 0.266

Asia WGS AF: 0.227 AC: 789 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.013
DANN	Benign	0.22
PhyloP100		-2.6
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: rs2297615; hg19: chr14-20846521; COSMIC: COSV52989727; COSMIC: COSV52989727;