chr14-20382104-G-A

Variant names:

• chr14-20382104-G-A
• rs11850456
• NM_007110.5:c.4274-41C>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.4274-41C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0463 in 1,611,580 control chromosomes in the GnomAD database, including 4,305 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 0.096 (1305 hom., cov: 32)
  • Exomes 𝑓: 0.041 (3000 hom.)
• Consequence: TEP1 NM_007110.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.206 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.4274-41C>T		intron	N/A	NP_009041.2
	TEP1	NM_001319035.2		c.3950-41C>T		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.4274-41C>T		intron	N/A	ENSP00000262715.5
	TEP1	ENST00000556935.5	TSL:1	c.3950-41C>T		intron	N/A	ENSP00000452574.1
	TEP1	ENST00000555008.5	TSL:1	n.2303-41C>T		intron	N/A	ENSP00000450541.1

Frequencies

GnomAD3 genomes AF: 0.0963 AC: 14624 AN: 151890 Hom.: 1299 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.0699

Gnomad FIN AF: 0.0261

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0247

Gnomad OTH AF: 0.0938

GnomAD2 exomes AF: 0.0789 AC: 19455 AN: 246490 AF XY: 0.0704

Gnomad AFR exome AF: 0.216

Gnomad AMR exome AF: 0.210

Gnomad ASJ exome AF: 0.0177

Gnomad EAS exome AF: 0.166

Gnomad FIN exome AF: 0.0237

Gnomad NFE exome AF: 0.0242

Gnomad OTH exome AF: 0.0639

GnomAD4 exome AF: 0.0411 AC: 60006 AN: 1459572 Hom.: 3000 Cov.: 34 AF XY: 0.0405 AC XY: 29424 AN XY: 725988

African (AFR) AF: 0.216 AC: 7225 AN: 33460

American (AMR) AF: 0.208 AC: 9243 AN: 44458

Ashkenazi Jewish (ASJ) AF: 0.0187 AC: 483 AN: 25860

East Asian (EAS) AF: 0.143 AC: 5668 AN: 39662

South Asian (SAS) AF: 0.0685 AC: 5896 AN: 86012

European-Finnish (FIN) AF: 0.0224 AC: 1194 AN: 53208

Middle Eastern (MID) AF: 0.0660 AC: 380 AN: 5758

European-Non Finnish (NFE) AF: 0.0240 AC: 26671 AN: 1110830

Other (OTH) AF: 0.0538 AC: 3246 AN: 60324

GnomAD4 genome AF: 0.0964 AC: 14658 AN: 152008 Hom.: 1305 Cov.: 32 AF XY: 0.0998 AC XY: 7417 AN XY: 74336

African (AFR) AF: 0.209 AC: 8668 AN: 41402

American (AMR) AF: 0.168 AC: 2561 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0153 AC: 53 AN: 3468

East Asian (EAS) AF: 0.168 AC: 871 AN: 5172

South Asian (SAS) AF: 0.0708 AC: 341 AN: 4818

European-Finnish (FIN) AF: 0.0261 AC: 276 AN: 10588

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0247 AC: 1682 AN: 67982

Other (OTH) AF: 0.0923 AC: 195 AN: 2112

Alfa AF: 0.0380 Hom.: 441

Bravo AF: 0.113

Asia WGS AF: 0.112 AC: 390 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.85
DANN	Benign	0.24
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs11850456; hg19: chr14-20850263; COSMIC: COSV53002657; COSMIC: COSV53002657;