chr4-105218230-T-C

Position:

• chr4-105218230-T-C

Variant summary

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

The NM_001127208.3(TET2):​c.-46-15667T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 152,048 control chromosomes in the GnomAD database, including 1,235 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 0.12 (1235 hom., cov: 32)
• Consequence: TET2 NM_001127208.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TET2	NM_001127208.3	c.-46-15667T>C		intron_variant		ENST00000380013.9	NP_001120680.1
TET2-AS1	NR_126420.1	n.319-40558A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TET2	ENST00000380013.9	c.-46-15667T>C		intron_variant		5	NM_001127208.3	ENSP00000369351	A2

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17779 AN: 151930 Hom.: 1234 Cov.: 32

Gnomad AFR AF: 0.0695

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.0904

Gnomad EAS AF: 0.00538

Gnomad SAS AF: 0.0656

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.117 AC: 17777 AN: 152048 Hom.: 1235 Cov.: 32 AF XY: 0.114 AC XY: 8439 AN XY: 74324

Gnomad4 AFR AF: 0.0695

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.0904

Gnomad4 EAS AF: 0.00539

Gnomad4 SAS AF: 0.0655

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.127

Alfa AF: 0.142 Hom.: 761

Bravo AF: 0.114

Asia WGS AF: 0.0380 AC: 135 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	0.067
DANN	Benign	0.72

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: rs4698934; hg19: chr4-106139387;