7-124822607-C-T

Variant names:

• chr7-124822607-C-T
• rs17246404
• NM_015450.3:c.*1355G>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.*1355G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 444,536 control chromosomes in the GnomAD database, including 13,337 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 0.20 (3816 hom., cov: 32)
  • Exomes 𝑓: 0.24 (9521 hom.)
• Consequence: POT1 NM_015450.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.658
• Publications: 35 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.29 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.*1355G>A		3_prime_UTR	Exon 19 of 19	NP_056265.2	Q9NUX5-1
	POT1	NM_001042594.2		c.*1355G>A		3_prime_UTR	Exon 18 of 18	NP_001036059.1	A8MTK3
	POT1	NR_003102.2		n.3823G>A		non_coding_transcript_exon	Exon 20 of 20

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POT1	ENST00000357628.8	TSL:2 MANE Select	c.*1355G>A		3_prime_UTR	Exon 19 of 19	ENSP00000350249.3	Q9NUX5-1
	POT1	ENST00000430927.6	TSL:3	n.*425-56G>A		intron	N/A	ENSP00000397632.2	Q5MJ34
	POT1	ENST00000436534.5	TSL:3	n.392-56G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30560 AN: 151786 Hom.: 3819 Cov.: 32

Gnomad AFR AF: 0.0549

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.202

GnomAD4 exome AF: 0.245 AC: 71567 AN: 292632 Hom.: 9521 Cov.: 0 AF XY: 0.244 AC XY: 40731 AN XY: 167074

African (AFR) AF: 0.0541 AC: 460 AN: 8508

American (AMR) AF: 0.167 AC: 4494 AN: 26980

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 3009 AN: 10360

East Asian (EAS) AF: 0.294 AC: 2679 AN: 9116

South Asian (SAS) AF: 0.200 AC: 11619 AN: 58090

European-Finnish (FIN) AF: 0.213 AC: 2641 AN: 12370

Middle Eastern (MID) AF: 0.221 AC: 602 AN: 2722

European-Non Finnish (NFE) AF: 0.283 AC: 42656 AN: 150922

Other (OTH) AF: 0.251 AC: 3407 AN: 13564

GnomAD4 genome AF: 0.201 AC: 30549 AN: 151904 Hom.: 3816 Cov.: 32 AF XY: 0.197 AC XY: 14652 AN XY: 74250

African (AFR) AF: 0.0548 AC: 2274 AN: 41494

American (AMR) AF: 0.184 AC: 2812 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 978 AN: 3470

East Asian (EAS) AF: 0.303 AC: 1565 AN: 5170

South Asian (SAS) AF: 0.184 AC: 889 AN: 4822

European-Finnish (FIN) AF: 0.201 AC: 2123 AN: 10552

Middle Eastern (MID) AF: 0.195 AC: 57 AN: 292

European-Non Finnish (NFE) AF: 0.283 AC: 19190 AN: 67840

Other (OTH) AF: 0.201 AC: 424 AN: 2110

Alfa AF: 0.248 Hom.: 13260

Bravo AF: 0.196

Asia WGS AF: 0.227 AC: 787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.46
DANN	Benign	0.32
PhyloP100		-0.66
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: rs17246404; hg19: chr7-124462661; COSMIC: COSV62930943; COSMIC: COSV62930943;