chr7-124825455-A-C

Variant names:

• chr7-124825455-A-C
• rs10250202
• NM_015450.3:c.1687-98T>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.1687-98T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 694,240 control chromosomes in the GnomAD database, including 57,063 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (12224 hom., cov: 32)
  • Exomes 𝑓: 0.40 (44839 hom.)
• Consequence: POT1 NM_015450.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.00300
• Publications: 10 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: Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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: Ambry Genetics, G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 7-124825455-A-C is Benign according to our data. Variant chr7-124825455-A-C is described in ClinVar as Benign. ClinVar VariationId is 677019.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.479 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.1687-98T>G		intron	N/A	NP_056265.2	Q9NUX5-1
	POT1	NM_001042594.2		c.1294-98T>G		intron	N/A	NP_001036059.1	A8MTK3
	POT1	NR_003102.2		n.2250-98T>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POT1	ENST00000357628.8	TSL:2 MANE Select	c.1687-98T>G		intron	N/A	ENSP00000350249.3	Q9NUX5-1
	POT1	ENST00000607932.5	TSL:1	n.*41-98T>G		intron	N/A	ENSP00000476506.1	Q5MJ34
	POT1	ENST00000608057.5	TSL:1	n.*784-98T>G		intron	N/A	ENSP00000476371.1	Q5MJ35

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60556 AN: 151824 Hom.: 12209 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: 0.495

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.391

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.429

GnomAD4 exome AF: 0.405 AC: 219467 AN: 542298 Hom.: 44839 AF XY: 0.404 AC XY: 113000 AN XY: 279884

African (AFR) AF: 0.349 AC: 4676 AN: 13398

American (AMR) AF: 0.448 AC: 7535 AN: 16818

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 5701 AN: 13774

East Asian (EAS) AF: 0.470 AC: 13279 AN: 28234

South Asian (SAS) AF: 0.385 AC: 12520 AN: 32504

European-Finnish (FIN) AF: 0.487 AC: 13879 AN: 28510

Middle Eastern (MID) AF: 0.344 AC: 701 AN: 2038

European-Non Finnish (NFE) AF: 0.395 AC: 149521 AN: 378902

Other (OTH) AF: 0.414 AC: 11655 AN: 28120

GnomAD4 genome AF: 0.399 AC: 60608 AN: 151942 Hom.: 12224 Cov.: 32 AF XY: 0.402 AC XY: 29879 AN XY: 74262

African (AFR) AF: 0.353 AC: 14618 AN: 41432

American (AMR) AF: 0.429 AC: 6545 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1382 AN: 3466

East Asian (EAS) AF: 0.495 AC: 2564 AN: 5176

South Asian (SAS) AF: 0.388 AC: 1869 AN: 4820

European-Finnish (FIN) AF: 0.502 AC: 5300 AN: 10550

Middle Eastern (MID) AF: 0.400 AC: 116 AN: 290

European-Non Finnish (NFE) AF: 0.395 AC: 26813 AN: 67922

Other (OTH) AF: 0.428 AC: 903 AN: 2110

Alfa AF: 0.391 Hom.: 2479

Bravo AF: 0.395

Asia WGS AF: 0.414 AC: 1435 AN: 3468

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.9
DANN	Benign	0.79
PhyloP100		-0.0030
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: rs10250202; hg19: chr7-124465509;