chr7-124822607-C-A

Variant names:

• chr7-124822607-C-A
• rs17246404
• NM_015450.3:c.*1355G>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS1

The NM_015450.3(POT1):​c.*1355G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000121 in 444,938 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00022 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000072 (0 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000217 (33/151830) while in subpopulation AMR AF = 0.00197 (30/15232). AF 95% confidence interval is 0.00142. There are 0 homozygotes in GnomAd4. There are 23 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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>T		3_prime_UTR	Exon 19 of 19	NP_056265.2	Q9NUX5-1
	POT1	NM_001042594.2		c.*1355G>T		3_prime_UTR	Exon 18 of 18	NP_001036059.1	A8MTK3
	POT1	NR_003102.2		n.3823G>T		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>T		3_prime_UTR	Exon 19 of 19	ENSP00000350249.3	Q9NUX5-1
	POT1	ENST00000430927.6	TSL:3	n.*425-56G>T		intron	N/A	ENSP00000397632.2	Q5MJ34
	POT1	ENST00000436534.5	TSL:3	n.392-56G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000217 AC: 33 AN: 151830 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000442

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000716 AC: 21 AN: 293108 Hom.: 0 Cov.: 0 AF XY: 0.0000777 AC XY: 13 AN XY: 167356

African (AFR) AF: 0.00 AC: 0 AN: 8512

American (AMR) AF: 0.000630 AC: 17 AN: 26996

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10368

East Asian (EAS) AF: 0.00 AC: 0 AN: 9122

South Asian (SAS) AF: 0.00 AC: 0 AN: 58178

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2722

European-Non Finnish (NFE) AF: 0.0000265 AC: 4 AN: 151226

Other (OTH) AF: 0.00 AC: 0 AN: 13594

GnomAD4 genome AF: 0.000217 AC: 33 AN: 151830 Hom.: 0 Cov.: 32 AF XY: 0.000310 AC XY: 23 AN XY: 74144

African (AFR) AF: 0.00 AC: 0 AN: 41376

American (AMR) AF: 0.00197 AC: 30 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10556

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000442 AC: 3 AN: 67876

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 13260

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.15
DANN	Benign	0.39
PhyloP100		-0.66
Mutation Taster		=100/0	polymorphism

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;