7-124825455-A-C

Position:

• chr7-124825455-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015450.3(POT1):​c.1687-98T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 694,240 control chromosomes in the GnomAD database, including 57,063 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (12224 hom., cov: 32)
  • Exomes 𝑓: 0.40 (44839 hom.)
• Consequence: POT1 NM_015450.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.00300

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 7-124825455-A-C is Benign according to our data. Variant chr7-124825455-A-C is described in ClinVar as [Benign]. Clinvar id is 677019.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POT1	NM_015450.3	c.1687-98T>G		intron_variant		ENST00000357628.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POT1	ENST00000357628.8	c.1687-98T>G		intron_variant		2	NM_015450.3	P1

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60556 AN: 151824 Hom.: 12209 Cov.: 32

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.391

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.429

GnomAD4 exome AF: 0.405 AC: 219467 AN: 542298 Hom.: 44839 AF XY: 0.404 AC XY: 113000 AN XY: 279884

Gnomad4 AFR exome AF: 0.349

Gnomad4 AMR exome AF: 0.448

Gnomad4 ASJ exome AF: 0.414

Gnomad4 EAS exome AF: 0.470

Gnomad4 SAS exome AF: 0.385

Gnomad4 FIN exome AF: 0.487

Gnomad4 NFE exome AF: 0.395

Gnomad4 OTH exome AF: 0.414

GnomAD4 genome AF: 0.399 AC: 60608 AN: 151942 Hom.: 12224 Cov.: 32 AF XY: 0.402 AC XY: 29879 AN XY: 74262

Gnomad4 AFR AF: 0.353

Gnomad4 AMR AF: 0.429

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.495

Gnomad4 SAS AF: 0.388

Gnomad4 FIN AF: 0.502

Gnomad4 NFE AF: 0.395

Gnomad4 OTH AF: 0.428

Alfa AF: 0.393 Hom.: 2437

Bravo AF: 0.395

Asia WGS AF: 0.414 AC: 1435 AN: 3468

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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 12, 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	-0.86
CADD	Benign	4.9
DANN	Benign	0.79

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: rs10250202; hg19: chr7-124465509;