7-124833771-C-T

Variant names:

• chr7-124833771-C-T
• rs2896361
• NM_015450.3:c.1505+1508G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015450.3(POT1):​c.1505+1508G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 152,028 control chromosomes in the GnomAD database, including 12,243 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 0.40 (12243 hom., cov: 32)
• Consequence: POT1 NM_015450.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.189
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POT1	NM_015450.3	c.1505+1508G>A		intron_variant	Intron 15 of 18	ENST00000357628.8	NP_056265.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POT1	ENST00000357628.8	c.1505+1508G>A		intron_variant	Intron 15 of 18	2	NM_015450.3	ENSP00000350249.3

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60614 AN: 151910 Hom.: 12228 Cov.: 32

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.430

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

GnomAD4 genome AF: 0.399 AC: 60666 AN: 152028 Hom.: 12243 Cov.: 32 AF XY: 0.403 AC XY: 29901 AN XY: 74288

African (AFR) AF: 0.353 AC: 14633 AN: 41492

American (AMR) AF: 0.429 AC: 6551 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1383 AN: 3466

East Asian (EAS) AF: 0.495 AC: 2555 AN: 5164

South Asian (SAS) AF: 0.388 AC: 1872 AN: 4824

European-Finnish (FIN) AF: 0.503 AC: 5302 AN: 10540

Middle Eastern (MID) AF: 0.401 AC: 117 AN: 292

European-Non Finnish (NFE) AF: 0.395 AC: 26848 AN: 67954

Other (OTH) AF: 0.429 AC: 907 AN: 2112

Alfa AF: 0.392 Hom.: 4032

Bravo AF: 0.395

Asia WGS AF: 0.415 AC: 1442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.0
DANN	Benign	0.50
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2896361; hg19: chr7-124473825;