rs7663401

Variant names:

• chr4-105207797-C-T
• rs7663401
• NM_001127208.3:c.-47+17292C>T

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+17292C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 151,780 control chromosomes in the GnomAD database, including 21,186 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 0.52 (21186 hom., cov: 32)
• Consequence: TET2 NM_001127208.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.739
• Publications: 12 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.609 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.-47+17292C>T		intron	N/A	NP_001120680.1	Q6N021-1
	TET2	NM_017628.4		c.-47+17292C>T		intron	N/A	NP_060098.3	Q6N021-2
	TET2-AS1	NR_126420.1		n.319-30125G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TET2	ENST00000380013.9	TSL:5 MANE Select	c.-47+17292C>T		intron	N/A	ENSP00000369351.4	Q6N021-1
	TET2	ENST00000513237.5	TSL:1	c.17+17311C>T		intron	N/A	ENSP00000425443.1	E7EQS8
	TET2	ENST00000540549.5	TSL:1	c.-47+17311C>T		intron	N/A	ENSP00000442788.1	Q6N021-1

Frequencies

GnomAD3 genomes AF: 0.520 AC: 78826 AN: 151662 Hom.: 21191 Cov.: 32

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.671

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.522

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

GnomAD4 genome AF: 0.519 AC: 78839 AN: 151780 Hom.: 21186 Cov.: 32 AF XY: 0.510 AC XY: 37859 AN XY: 74178

African (AFR) AF: 0.415 AC: 17170 AN: 41342

American (AMR) AF: 0.484 AC: 7382 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 1619 AN: 3468

East Asian (EAS) AF: 0.276 AC: 1424 AN: 5160

South Asian (SAS) AF: 0.413 AC: 1988 AN: 4816

European-Finnish (FIN) AF: 0.542 AC: 5719 AN: 10550

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.614 AC: 41710 AN: 67900

Other (OTH) AF: 0.514 AC: 1080 AN: 2100

Alfa AF: 0.589 Hom.: 11730

Bravo AF: 0.510

Asia WGS AF: 0.363 AC: 1266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.4
DANN	Benign	0.32
PhyloP100		0.74
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: rs7663401; hg19: chr4-106128954;