rs949681

chr4-105209868-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001127208.3(TET2):c.-47+19363G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0399 in 152,168 control chromosomes in the GnomAD database, including 266 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 0.040 (266 hom., cov: 31)
• Consequence: TET2 NM_001127208.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.246

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TET2	NM_001127208.3	c.-47+19363G>A		intron_variant		ENST00000380013.9
TET2-AS1	NR_126420.1	n.319-32196C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TET2	ENST00000380013.9	c.-47+19363G>A		intron_variant		5	NM_001127208.3	A2

Frequencies

GnomAD3 genomes AF: 0.0398 AC: 6058 AN: 152050 Hom.: 264 Cov.: 31

Gnomad AFR AF: 0.0315

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0724

Gnomad ASJ AF: 0.0309

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.0689

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0169

Gnomad OTH AF: 0.0435

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

GnomAD4 genome AF: 0.0399 AC: 6067 AN: 152168 Hom.: 266 Cov.: 31 AF XY: 0.0448 AC XY: 3337 AN XY: 74416

Gnomad4 AFR AF: 0.0316

Gnomad4 AMR AF: 0.0730

Gnomad4 ASJ AF: 0.0309

Gnomad4 EAS AF: 0.189

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.0689

Gnomad4 NFE AF: 0.0169

Gnomad4 OTH AF: 0.0430

Alfa AF: 0.0329 Hom.: 25

Bravo AF: 0.0418

Asia WGS AF: 0.135 AC: 468 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.7
Dann	Benign	0.71

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: rs949681; hg19: chr4-106131025;