rs372566252

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_015450.3(POT1):c.870-7A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,426,264 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

POT1
NM_015450.3 splice_region, intron

Scores

Splicing: ADA: 0.00005842

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0590

Publications

0 publications found

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]

POT1 Gene-Disease associations (from GenCC):

pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 8
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
tumor predisposition syndrome 3
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
glioma susceptibility 9
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
thyroid gland carcinoma
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
cerebroretinal microangiopathy with calcifications and cysts 3
Inheritance: AR Classification: LIMITED Submitted by: G2P, Ambry Genetics

POT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 7-124851958-T-A is Benign according to our data. Variant chr7-124851958-T-A is described in CliVar as Likely_benign. Clinvar id is 1573915.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-124851958-T-A is described in CliVar as Likely_benign. Clinvar id is 1573915.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-124851958-T-A is described in CliVar as Likely_benign. Clinvar id is 1573915.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-124851958-T-A is described in CliVar as Likely_benign. Clinvar id is 1573915.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-124851958-T-A is described in CliVar as Likely_benign. Clinvar id is 1573915.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-124851958-T-A is described in CliVar as Likely_benign. Clinvar id is 1573915.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-124851958-T-A is described in CliVar as Likely_benign. Clinvar id is 1573915.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-124851958-T-A is described in CliVar as Likely_benign. Clinvar id is 1573915.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-124851958-T-A is described in CliVar as Likely_benign. Clinvar id is 1573915.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-124851958-T-A is described in CliVar as Likely_benign. Clinvar id is 1573915.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-124851958-T-A is described in CliVar as Likely_benign. Clinvar id is 1573915.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-124851958-T-A is described in CliVar as Likely_benign. Clinvar id is 1573915.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-124851958-T-A is described in CliVar as Likely_benign. Clinvar id is 1573915.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-124851958-T-A is described in CliVar as Likely_benign. Clinvar id is 1573915.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-124851958-T-A is described in CliVar as Likely_benign. Clinvar id is 1573915.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-124851958-T-A is described in CliVar as Likely_benign. Clinvar id is 1573915.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-124851958-T-A is described in CliVar as Likely_benign. Clinvar id is 1573915.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-124851958-T-A is described in CliVar as Likely_benign. Clinvar id is 1573915.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-124851958-T-A is described in CliVar as Likely_benign. Clinvar id is 1573915.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-124851958-T-A is described in CliVar as Likely_benign. Clinvar id is 1573915.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-124851958-T-A is described in CliVar as Likely_benign. Clinvar id is 1573915.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-124851958-T-A is described in CliVar as Likely_benign. Clinvar id is 1573915.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POT1	NM_015450.3 link	c.870-7A>T		splice_region_variant, intron_variant	Intron 10 of 18	ENST00000357628.8	NP_056265.2	Q9NUX5-1A0A024R739

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POT1	ENST00000357628.8 link	c.870-7A>T		splice_region_variant, intron_variant	Intron 10 of 18	2	NM_015450.3	ENSP00000350249.3		Q9NUX5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000403

AC:

AN:

248116

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.00000140

AC:

AN:

1426264

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

711622

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32648

American (AMR)

AF:

0.00

AC:

AN:

44338

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25822

East Asian (EAS)

AF:

0.00

AC:

AN:

39352

South Asian (SAS)

AF:

0.00

AC:

AN:

84770

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53362

Middle Eastern (MID)

AF:

0.000182

AC:

AN:

5494

European-Non Finnish (NFE)

AF:

9.25e-7

AC:

AN:

1081292

Other (OTH)

AF:

0.00

AC:

AN:

59186

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.000111

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Tumor predisposition syndrome 3

Benign:1

May 08, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

8.3

(source)

DANN

Benign

0.64

PhyloP100

0.059

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000058

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over