rs4360236

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015450.3(POT1):​c.124+5581G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 151,856 control chromosomes in the GnomAD database, including 3,095 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 0.18 ( 3095 hom., cov: 32)

Consequence

POT1
NM_015450.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.12
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
POT1NM_015450.3 linkuse as main transcriptc.124+5581G>A intron_variant ENST00000357628.8 NP_056265.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
POT1ENST00000357628.8 linkuse as main transcriptc.124+5581G>A intron_variant 2 NM_015450.3 ENSP00000350249 P1Q9NUX5-1

Frequencies

GnomAD3 genomes
AF:
0.183
AC:
27828
AN:
151738
Hom.:
3090
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.303
Gnomad AMI
AF:
0.0899
Gnomad AMR
AF:
0.234
Gnomad ASJ
AF:
0.130
Gnomad EAS
AF:
0.200
Gnomad SAS
AF:
0.294
Gnomad FIN
AF:
0.100
Gnomad MID
AF:
0.158
Gnomad NFE
AF:
0.108
Gnomad OTH
AF:
0.168
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.184
AC:
27867
AN:
151856
Hom.:
3095
Cov.:
32
AF XY:
0.188
AC XY:
13941
AN XY:
74206
show subpopulations
Gnomad4 AFR
AF:
0.302
Gnomad4 AMR
AF:
0.234
Gnomad4 ASJ
AF:
0.130
Gnomad4 EAS
AF:
0.200
Gnomad4 SAS
AF:
0.293
Gnomad4 FIN
AF:
0.100
Gnomad4 NFE
AF:
0.108
Gnomad4 OTH
AF:
0.174
Alfa
AF:
0.130
Hom.:
2300
Bravo
AF:
0.194
Asia WGS
AF:
0.272
AC:
944
AN:
3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
3.7
DANN
Benign
0.53

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs4360236; hg19: chr7-124526739; API