4-105218230-T-C

Variant names:

• chr4-105218230-T-C
• rs4698934
• NM_001127208.3:c.-46-15667T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127208.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TET2	NM_001127208.3	MANE Select	c.-46-15667T>C		intron	N/A	NP_001120680.1	Q6N021-1
	TET2	NM_017628.4		c.-46-15667T>C		intron	N/A	NP_060098.3	Q6N021-2
	TET2-AS1	NR_126420.1		n.319-40558A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TET2	ENST00000380013.9	TSL:5 MANE Select	c.-46-15667T>C		intron	N/A	ENSP00000369351.4	Q6N021-1
	TET2	ENST00000513237.5	TSL:1	c.18-15667T>C		intron	N/A	ENSP00000425443.1	E7EQS8
	TET2	ENST00000540549.5	TSL:1	c.-46-15667T>C		intron	N/A	ENSP00000442788.1	Q6N021-1

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

African (AFR) AF: 0.0695 AC: 2885 AN: 41514

American (AMR) AF: 0.112 AC: 1715 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0904 AC: 313 AN: 3464

East Asian (EAS) AF: 0.00539 AC: 28 AN: 5194

South Asian (SAS) AF: 0.0655 AC: 316 AN: 4826

European-Finnish (FIN) AF: 0.122 AC: 1289 AN: 10576

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10686 AN: 67894

Other (OTH) AF: 0.127 AC: 268 AN: 2112

Alfa AF: 0.141 Hom.: 854

Bravo AF: 0.114

Asia WGS AF: 0.0380 AC: 135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.067
DANN	Benign	0.72
PhyloP100		-1.4
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: rs4698934; hg19: chr4-106139387;