chr7-124833771-C-T

Position:

• chr7-124833771-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015450.3(POT1):​c.1505+1508G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 152,028 control chromosomes in the GnomAD database, including 12,243 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 0.40 (12243 hom., cov: 32)
• Consequence: POT1 NM_015450.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.189

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• 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	Protein	UniProt
POT1	NM_015450.3	c.1505+1508G>A		intron_variant		ENST00000357628.8	NP_056265.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POT1	ENST00000357628.8	c.1505+1508G>A		intron_variant		2	NM_015450.3	ENSP00000350249.3

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60614 AN: 151910 Hom.: 12228 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: 0.494

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.430

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

GnomAD4 genome AF: 0.399 AC: 60666 AN: 152028 Hom.: 12243 Cov.: 32 AF XY: 0.403 AC XY: 29901 AN XY: 74288

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: 0.503

Gnomad4 NFE AF: 0.395

Gnomad4 OTH AF: 0.429

Alfa AF: 0.394 Hom.: 2414

Bravo AF: 0.395

Asia WGS AF: 0.415 AC: 1442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.0
DANN	Benign	0.50

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: rs2896361; hg19: chr7-124473825;