rs929365

Positions:

• chr7-124824377-T-C
• chr7-124824377-T-G

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.1793-303A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0344 in 152,112 control chromosomes in the GnomAD database, including 116 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.034 (116 hom., cov: 32)
• Consequence: POT1 NM_015450.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.861

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 7-124824377-T-C is Benign according to our data. Variant chr7-124824377-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1192050.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.051 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POT1	NM_015450.3	c.1793-303A>G		intron_variant		ENST00000357628.8	NP_056265.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POT1	ENST00000357628.8	c.1793-303A>G		intron_variant		2	NM_015450.3	ENSP00000350249.3

Frequencies

GnomAD3 genomes AF: 0.0344 AC: 5229 AN: 151994 Hom.: 116 Cov.: 32

Gnomad AFR AF: 0.00951

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.0276

Gnomad ASJ AF: 0.0357

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0284

Gnomad FIN AF: 0.0389

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0524

Gnomad OTH AF: 0.0283

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0344 AC: 5230 AN: 152112 Hom.: 116 Cov.: 32 AF XY: 0.0338 AC XY: 2517 AN XY: 74362

Gnomad4 AFR AF: 0.00948

Gnomad4 AMR AF: 0.0275

Gnomad4 ASJ AF: 0.0357

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0286

Gnomad4 FIN AF: 0.0389

Gnomad4 NFE AF: 0.0525

Gnomad4 OTH AF: 0.0280

Alfa AF: 0.0459 Hom.: 42

Bravo AF: 0.0327

Asia WGS AF: 0.0160 AC: 56 AN: 3472

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 04, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.4
DANN	Benign	0.67

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: rs929365; hg19: chr7-124464431;