rs1391442

Variant names:

• chr4-105211163-A-G
• rs1391442
• NM_001127208.3:c.-47+20658A>G

Variant summary

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

The NM_001127208.3(TET2):​c.-47+20658A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0828 in 152,206 control chromosomes in the GnomAD database, including 957 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 0.083 (957 hom., cov: 32)
• Consequence: TET2 NM_001127208.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.761
• Publications: 1 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-AS1 (HGNC:41125): (TET2 antisense RNA 1)

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 = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TET2	NM_001127208.3	c.-47+20658A>G		intron_variant	Intron 2 of 10	ENST00000380013.9	NP_001120680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TET2	ENST00000380013.9	c.-47+20658A>G		intron_variant	Intron 2 of 10	5	NM_001127208.3	ENSP00000369351.4

Frequencies

GnomAD3 genomes AF: 0.0827 AC: 12573 AN: 152088 Hom.: 956 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0902

Gnomad ASJ AF: 0.0326

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.0687

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0172

Gnomad OTH AF: 0.0684

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

GnomAD4 genome AF: 0.0828 AC: 12602 AN: 152206 Hom.: 957 Cov.: 32 AF XY: 0.0864 AC XY: 6426 AN XY: 74416

African (AFR) AF: 0.179 AC: 7437 AN: 41486

American (AMR) AF: 0.0908 AC: 1389 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0326 AC: 113 AN: 3470

East Asian (EAS) AF: 0.196 AC: 1019 AN: 5186

South Asian (SAS) AF: 0.122 AC: 587 AN: 4822

European-Finnish (FIN) AF: 0.0687 AC: 729 AN: 10608

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0172 AC: 1171 AN: 68020

Other (OTH) AF: 0.0676 AC: 143 AN: 2114

Alfa AF: 0.0592 Hom.: 82

Bravo AF: 0.0910

Asia WGS AF: 0.147 AC: 509 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	3.9
DANN	Benign	0.66
PhyloP100		0.76
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: rs1391442; hg19: chr4-106132320;