rs1391441

chr4-105207603-G-Achr4-105207603-G-C

Variant summary

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

The NM_001127208.3(TET2):c.-47+17098G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.696 in 151,752 control chromosomes in the GnomAD database, including 37,554 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 0.70 (37554 hom., cov: 30)
• Consequence: TET2 NM_001127208.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TET2	NM_001127208.3	c.-47+17098G>A		intron_variant		ENST00000380013.9
TET2-AS1	NR_126420.1	n.319-29931C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TET2	ENST00000380013.9	c.-47+17098G>A		intron_variant		5	NM_001127208.3	A2

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105534 AN: 151632 Hom.: 37509 Cov.: 30

Gnomad AFR AF: 0.846

Gnomad AMI AF: 0.698

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.662

Gnomad OTH AF: 0.672

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

GnomAD4 genome AF: 0.696 AC: 105628 AN: 151752 Hom.: 37554 Cov.: 30 AF XY: 0.688 AC XY: 50972 AN XY: 74124

Gnomad4 AFR AF: 0.846

Gnomad4 AMR AF: 0.627

Gnomad4 ASJ AF: 0.590

Gnomad4 EAS AF: 0.473

Gnomad4 SAS AF: 0.582

Gnomad4 FIN AF: 0.633

Gnomad4 NFE AF: 0.662

Gnomad4 OTH AF: 0.663

Alfa AF: 0.668 Hom.: 20032

Bravo AF: 0.704

Asia WGS AF: 0.552 AC: 1923 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.10
Dann	Benign	0.37

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: rs1391441; hg19: chr4-106128760;