rs11972248

Variant names:

• chr7-124848956-T-C
• rs11972248
• NM_015450.3:c.950-1958A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-124848956-T-C
• chr7-124848956-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015450.3(POT1):​c.950-1958A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,156 control chromosomes in the GnomAD database, including 2,058 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 0.16 (2058 hom., cov: 33)
• Consequence: POT1 NM_015450.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.2 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POT1	NM_015450.3	MANE Select	c.950-1958A>G		intron	N/A	NP_056265.2
	POT1	NM_001042594.2		c.557-1958A>G		intron	N/A	NP_001036059.1
	POT1	NR_003102.2		n.1393-297A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POT1	ENST00000357628.8	TSL:2 MANE Select	c.950-1958A>G		intron	N/A	ENSP00000350249.3
	POT1	ENST00000607932.5	TSL:1	n.950-1958A>G		intron	N/A	ENSP00000476506.1
	POT1	ENST00000608057.5	TSL:1	n.950-297A>G		intron	N/A	ENSP00000476371.1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23643 AN: 152038 Hom.: 2058 Cov.: 33

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.153

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.155 AC: 23640 AN: 152156 Hom.: 2058 Cov.: 33 AF XY: 0.151 AC XY: 11267 AN XY: 74388

African (AFR) AF: 0.109 AC: 4537 AN: 41534

American (AMR) AF: 0.114 AC: 1741 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 583 AN: 3468

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5182

South Asian (SAS) AF: 0.102 AC: 493 AN: 4830

European-Finnish (FIN) AF: 0.194 AC: 2048 AN: 10560

Middle Eastern (MID) AF: 0.154 AC: 45 AN: 292

European-Non Finnish (NFE) AF: 0.203 AC: 13792 AN: 67992

Other (OTH) AF: 0.143 AC: 302 AN: 2110

Alfa AF: 0.173 Hom.: 1916

Bravo AF: 0.147

Asia WGS AF: 0.0500 AC: 173 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.11
DANN	Benign	0.77
PhyloP100		-1.7
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: rs11972248; hg19: chr7-124489010;