rs6973812

Positions:

• chr7-124866696-T-C

Variant summary

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

The NM_015450.3(POT1):​c.256-3056A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 152,012 control chromosomes in the GnomAD database, including 27,610 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 0.60 (27610 hom., cov: 32)
• Consequence: POT1 NM_015450.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.593

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POT1	NM_015450.3	c.256-3056A>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.256-3056A>G		intron_variant		2	NM_015450.3	ENSP00000350249	P1

Frequencies

GnomAD3 genomes AF: 0.601 AC: 91332 AN: 151894 Hom.: 27588 Cov.: 32

Gnomad AFR AF: 0.648

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.572

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

GnomAD4 genome AF: 0.601 AC: 91398 AN: 152012 Hom.: 27610 Cov.: 32 AF XY: 0.598 AC XY: 44406 AN XY: 74270

Gnomad4 AFR AF: 0.648

Gnomad4 AMR AF: 0.571

Gnomad4 ASJ AF: 0.601

Gnomad4 EAS AF: 0.504

Gnomad4 SAS AF: 0.614

Gnomad4 FIN AF: 0.498

Gnomad4 NFE AF: 0.605

Gnomad4 OTH AF: 0.573

Alfa AF: 0.612 Hom.: 13126

Bravo AF: 0.605

Asia WGS AF: 0.585 AC: 2037 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.80
DANN	Benign	0.82

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: rs6973812; hg19: chr7-124506750;