rs33964002

Variant names:

• chr7-124898561-C-T
• rs33964002
• NM_015450.3:c.-153-187G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015450.3(POT1):​c.-153-187G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 151,810 control chromosomes in the GnomAD database, including 7,750 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.32 (7750 hom., cov: 32)
• Consequence: POT1 NM_015450.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0130
• Publications: 6 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 7-124898561-C-T is Benign according to our data. Variant chr7-124898561-C-T is described in ClinVar as Benign. ClinVar VariationId is 678869.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015450.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POT1	NM_015450.3	MANE Select	c.-153-187G>A		intron	N/A	NP_056265.2	Q9NUX5-1
	POT1	NM_001042594.2		c.-415-187G>A		intron	N/A	NP_001036059.1	A8MTK3
	POT1	NR_003102.2		n.291-187G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POT1	ENST00000357628.8	TSL:2 MANE Select	c.-153-187G>A		intron	N/A	ENSP00000350249.3	Q9NUX5-1
	POT1	ENST00000653241.1		c.-153-187G>A		intron	N/A	ENSP00000499476.1	Q9NUX5-1
	POT1	ENST00000655761.1		c.-289-187G>A		intron	N/A	ENSP00000499635.1	Q9NUX5-1

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48418 AN: 151692 Hom.: 7746 Cov.: 32

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.295

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

GnomAD4 genome AF: 0.319 AC: 48449 AN: 151810 Hom.: 7750 Cov.: 32 AF XY: 0.321 AC XY: 23790 AN XY: 74174

African (AFR) AF: 0.340 AC: 14100 AN: 41442

American (AMR) AF: 0.342 AC: 5206 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1016 AN: 3466

East Asian (EAS) AF: 0.201 AC: 1036 AN: 5152

South Asian (SAS) AF: 0.395 AC: 1903 AN: 4818

European-Finnish (FIN) AF: 0.295 AC: 3100 AN: 10524

Middle Eastern (MID) AF: 0.305 AC: 89 AN: 292

European-Non Finnish (NFE) AF: 0.312 AC: 21198 AN: 67890

Other (OTH) AF: 0.297 AC: 625 AN: 2104

Alfa AF: 0.325 Hom.: 1083

Bravo AF: 0.319

Asia WGS AF: 0.318 AC: 1105 AN: 3470

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.4
DANN	Benign	0.72
PhyloP100		-0.013
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: rs33964002; hg19: chr7-124538615;