rs7663401

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TET2	NM_001127208.3	c.-47+17292C>T		intron_variant	Intron 2 of 10	ENST00000380013.9	NP_001120680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TET2	ENST00000380013.9	c.-47+17292C>T		intron_variant	Intron 2 of 10	5	NM_001127208.3	ENSP00000369351.4

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

Gnomad4 AFR AF: 0.415

Gnomad4 AMR AF: 0.484

Gnomad4 ASJ AF: 0.467

Gnomad4 EAS AF: 0.276

Gnomad4 SAS AF: 0.413

Gnomad4 FIN AF: 0.542

Gnomad4 NFE AF: 0.614

Gnomad4 OTH AF: 0.514

Alfa AF: 0.583 Hom.: 6196

Bravo AF: 0.510

Asia WGS AF: 0.363 AC: 1266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.4
DANN	Benign	0.32

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: rs7663401; hg19: chr4-106128954;