rs11972248

Positions:

• chr7-124848956-T-C
• chr7-124848956-T-G

Variant summary

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

The NM_015450.3(POT1):​c.950-1958A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,156 control chromosomes in the GnomAD database, including 2,058 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 0.16 (2058 hom., cov: 33)
• Consequence: POT1 NM_015450.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POT1	NM_015450.3	c.950-1958A>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.950-1958A>G		intron_variant		2	NM_015450.3	ENSP00000350249	P1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23643 AN: 152038 Hom.: 2058 Cov.: 33

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.153

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.155 AC: 23640 AN: 152156 Hom.: 2058 Cov.: 33 AF XY: 0.151 AC XY: 11267 AN XY: 74388

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.143

Alfa AF: 0.160 Hom.: 872

Bravo AF: 0.147

Asia WGS AF: 0.0500 AC: 173 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.11
DANN	Benign	0.77

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: rs11972248; hg19: chr7-124489010;