chr7-124846926-T-C

Variant names:

• chr7-124846926-T-C
• rs7794637
• NM_015450.3:c.1006+16A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015450.3(POT1):​c.1006+16A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 1,541,844 control chromosomes in the GnomAD database, including 363,760 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.71 (37967 hom., cov: 31)
  • Exomes 𝑓: 0.68 (325793 hom.)
• Consequence: POT1 NM_015450.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.81
• Publications: 16 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 7-124846926-T-C is Benign according to our data. Variant chr7-124846926-T-C is described in ClinVar as Benign. ClinVar VariationId is 516585.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POT1	NM_015450.3	c.1006+16A>G		intron_variant	Intron 12 of 18	ENST00000357628.8	NP_056265.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POT1	ENST00000357628.8	c.1006+16A>G		intron_variant	Intron 12 of 18	2	NM_015450.3	ENSP00000350249.3

Frequencies

GnomAD3 genomes AF: 0.706 AC: 107227 AN: 151852 Hom.: 37931 Cov.: 31

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.807

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.708

Gnomad EAS AF: 0.802

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.707

Gnomad MID AF: 0.707

Gnomad NFE AF: 0.691

Gnomad OTH AF: 0.728

GnomAD2 exomes AF: 0.694 AC: 173388 AN: 249916 AF XY: 0.690

Gnomad AFR exome AF: 0.734

Gnomad AMR exome AF: 0.681

Gnomad ASJ exome AF: 0.718

Gnomad EAS exome AF: 0.800

Gnomad FIN exome AF: 0.713

Gnomad NFE exome AF: 0.690

Gnomad OTH exome AF: 0.701

GnomAD4 exome AF: 0.683 AC: 949763 AN: 1389872 Hom.: 325793 Cov.: 24 AF XY: 0.682 AC XY: 473811 AN XY: 695218

African (AFR) AF: 0.729 AC: 23218 AN: 31830

American (AMR) AF: 0.682 AC: 30324 AN: 44434

Ashkenazi Jewish (ASJ) AF: 0.714 AC: 18344 AN: 25676

East Asian (EAS) AF: 0.792 AC: 31060 AN: 39208

South Asian (SAS) AF: 0.612 AC: 51765 AN: 84516

European-Finnish (FIN) AF: 0.709 AC: 37730 AN: 53204

Middle Eastern (MID) AF: 0.676 AC: 3792 AN: 5612

European-Non Finnish (NFE) AF: 0.681 AC: 713273 AN: 1047332

Other (OTH) AF: 0.693 AC: 40257 AN: 58060

GnomAD4 genome AF: 0.706 AC: 107321 AN: 151972 Hom.: 37967 Cov.: 31 AF XY: 0.705 AC XY: 52344 AN XY: 74266

African (AFR) AF: 0.733 AC: 30388 AN: 41444

American (AMR) AF: 0.691 AC: 10560 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.708 AC: 2453 AN: 3466

East Asian (EAS) AF: 0.802 AC: 4111 AN: 5128

South Asian (SAS) AF: 0.605 AC: 2914 AN: 4818

European-Finnish (FIN) AF: 0.707 AC: 7461 AN: 10558

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.691 AC: 46966 AN: 67966

Other (OTH) AF: 0.726 AC: 1529 AN: 2106

Alfa AF: 0.687 Hom.: 19743

Bravo AF: 0.712

Asia WGS AF: 0.691 AC: 2401 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Oct 11, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Tumor predisposition syndrome 3 Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: 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	-0.91
CADD	Benign	0.010
DANN	Benign	0.37
PhyloP100		-3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs7794637; hg19: chr7-124486980;