Variant rs7784168 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.722

Variant links:

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]

POT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
POT1	NM_015450.3 linkuse as main transcript	c.870-33A>G		intron_variant		ENST00000357628.8	NP_056265.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POT1	ENST00000357628.8 linkuse as main transcript	c.870-33A>G		intron_variant		2	NM_015450.3	ENSP00000350249	P1	Q9NUX5-1

Frequencies

GnomAD3 genomes

AF:

0.318

AC:

48275

AN:

151934

Hom.:

7700

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.319

AC XY:

201971

AN XY:

633462

show subpopulations

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.:

AF XY:

0.319

AC XY:

23734

AN XY:

74316

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over