rs9790517

Variant names:

• chr4-105163621-C-T
• rs9790517
• NM_001127208.3:c.-193+16642C>T

Variant summary

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

The NM_001127208.3(TET2):​c.-193+16642C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 152,044 control chromosomes in the GnomAD database, including 4,150 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 0.21 (4150 hom., cov: 31)
• Consequence: TET2 NM_001127208.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.436
• Publications: 79 publications found

Genes affected

TET2 (HGNC:25941): (tet methylcytosine dioxygenase 2) The protein encoded by this gene is a methylcytosine dioxygenase that catalyzes the conversion of methylcytosine to 5-hydroxymethylcytosine. The encoded protein is involved in myelopoiesis, and defects in this gene have been associated with several myeloproliferative disorders. Two variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2011]

TET2 Gene-Disease associations (from GenCC):

• immunodeficiency 75

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• pulmonary arterial hypertension

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen

LOC124900868 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TET2	NM_001127208.3	c.-193+16642C>T		intron_variant	Intron 1 of 10	ENST00000380013.9	NP_001120680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TET2	ENST00000380013.9	c.-193+16642C>T		intron_variant	Intron 1 of 10	5	NM_001127208.3	ENSP00000369351.4

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31140 AN: 151926 Hom.: 4138 Cov.: 31

Gnomad AFR AF: 0.0677

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.189

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.205 AC: 31173 AN: 152044 Hom.: 4150 Cov.: 31 AF XY: 0.212 AC XY: 15781 AN XY: 74310

African (AFR) AF: 0.0678 AC: 2814 AN: 41498

American (AMR) AF: 0.272 AC: 4158 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 918 AN: 3470

East Asian (EAS) AF: 0.617 AC: 3174 AN: 5144

South Asian (SAS) AF: 0.298 AC: 1438 AN: 4826

European-Finnish (FIN) AF: 0.245 AC: 2586 AN: 10548

Middle Eastern (MID) AF: 0.190 AC: 55 AN: 290

European-Non Finnish (NFE) AF: 0.227 AC: 15401 AN: 67960

Other (OTH) AF: 0.224 AC: 474 AN: 2112

Alfa AF: 0.222 Hom.: 11996

Bravo AF: 0.200

Asia WGS AF: 0.437 AC: 1516 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.9
DANN	Benign	0.42
PhyloP100		-0.44
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: rs9790517; hg19: chr4-106084778;