7-124822607-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POT1	NM_015450.3	c.*1355G>A		3_prime_UTR_variant	19/19	ENST00000357628.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POT1	ENST00000357628.8	c.*1355G>A		3_prime_UTR_variant	19/19	2	NM_015450.3	P1
POT1	ENST00000393329.5	c.*1355G>A		3_prime_UTR_variant	18/18	5
POT1	ENST00000430927.6	c.*425-56G>A		intron_variant, NMD_transcript_variant		3
POT1	ENST00000436534.5	n.392-56G>A		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR exome AF: 0.0541

Gnomad4 AMR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.290

Gnomad4 EAS exome AF: 0.294

Gnomad4 SAS exome AF: 0.200

Gnomad4 FIN exome AF: 0.213

Gnomad4 NFE exome AF: 0.283

Gnomad4 OTH exome AF: 0.251

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

Gnomad4 AFR AF: 0.0548

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.282

Gnomad4 EAS AF: 0.303

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.201

Alfa AF: 0.258 Hom.: 4681

Bravo AF: 0.196

Asia WGS AF: 0.227 AC: 787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.46
Dann	Benign	0.32

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

Publications

LitVar

Other links and lift over

dbSNP: rs17246404; hg19: chr7-124462661; COSMIC: COSV62930943; COSMIC: COSV62930943;