rs7784168

Positions:

• chr7-124851984-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015450.3(POT1):​c.870-33A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 1,406,024 control chromosomes in the GnomAD database, including 72,118 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (7704 hom., cov: 33)
  • Exomes 𝑓: 0.32 (64414 hom.)
• Consequence: POT1 NM_015450.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.722

Genes affected

POT1 (HGNC:17284): (protection of telomeres 1) This gene is a member of the telombin family and encodes a nuclear protein involved in telomere maintenance. Specifically, this protein functions as a member of a multi-protein complex that binds to the TTAGGG repeats of telomeres, regulating telomere length and protecting chromosome ends from illegitimate recombination, catastrophic chromosome instability, and abnormal chromosome segregation. Increased transcriptional expression of this gene is associated with stomach carcinogenesis and its progression. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 7-124851984-T-C is Benign according to our data. Variant chr7-124851984-T-C is described in ClinVar as [Benign]. Clinvar id is 677012.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POT1	NM_015450.3	c.870-33A>G		intron_variant		ENST00000357628.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POT1	ENST00000357628.8	c.870-33A>G		intron_variant		2	NM_015450.3	P1

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48275 AN: 151934 Hom.: 7700 Cov.: 33

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.292

GnomAD3 exomes AF: 0.323 AC: 75446 AN: 233736 Hom.: 12175 AF XY: 0.323 AC XY: 40702 AN XY: 126082

Gnomad AFR exome AF: 0.343

Gnomad AMR exome AF: 0.377

Gnomad ASJ exome AF: 0.287

Gnomad EAS exome AF: 0.205

Gnomad SAS exome AF: 0.392

Gnomad FIN exome AF: 0.290

Gnomad NFE exome AF: 0.316

Gnomad OTH exome AF: 0.308

GnomAD4 exome AF: 0.317 AC: 397648 AN: 1253972 Hom.: 64414 Cov.: 17 AF XY: 0.319 AC XY: 201971 AN XY: 633462

Gnomad4 AFR exome AF: 0.346

Gnomad4 AMR exome AF: 0.367

Gnomad4 ASJ exome AF: 0.285

Gnomad4 EAS exome AF: 0.211

Gnomad4 SAS exome AF: 0.387

Gnomad4 FIN exome AF: 0.292

Gnomad4 NFE exome AF: 0.315

Gnomad4 OTH exome AF: 0.310

GnomAD4 genome AF: 0.318 AC: 48306 AN: 152052 Hom.: 7704 Cov.: 33 AF XY: 0.319 AC XY: 23734 AN XY: 74316

Gnomad4 AFR AF: 0.340

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.201

Gnomad4 SAS AF: 0.395

Gnomad4 FIN AF: 0.294

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.294

Alfa AF: 0.318 Hom.: 4018

Bravo AF: 0.317

Asia WGS AF: 0.318 AC: 1107 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 20, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.98
DANN	Benign	0.90

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

Publications

LitVar

Other links and lift over

dbSNP: rs7784168; hg19: chr7-124492038; COSMIC: COSV62930379;