rs10010325

Variant names:

• chr4-105185196-C-A
• rs10010325
• NM_001127208.3:c.-192-5164C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-105185196-C-A
• chr4-105185196-C-G
• chr4-105185196-C-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.-192-5164C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 151,020 control chromosomes in the GnomAD database, including 18,172 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 0.49 (18172 hom., cov: 29)
• Consequence: TET2 NM_001127208.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.611
• Publications: 44 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TET2	NM_001127208.3	c.-192-5164C>A		intron_variant	Intron 1 of 10	ENST00000380013.9	NP_001120680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TET2	ENST00000380013.9	c.-192-5164C>A		intron_variant	Intron 1 of 10	5	NM_001127208.3	ENSP00000369351.4

Frequencies

GnomAD3 genomes AF: 0.490 AC: 73967 AN: 150902 Hom.: 18148 Cov.: 29

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.429

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.490 AC: 74033 AN: 151020 Hom.: 18172 Cov.: 29 AF XY: 0.489 AC XY: 36030 AN XY: 73722

African (AFR) AF: 0.480 AC: 19725 AN: 41130

American (AMR) AF: 0.523 AC: 7955 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 1602 AN: 3462

East Asian (EAS) AF: 0.550 AC: 2815 AN: 5120

South Asian (SAS) AF: 0.452 AC: 2162 AN: 4780

European-Finnish (FIN) AF: 0.425 AC: 4384 AN: 10308

Middle Eastern (MID) AF: 0.428 AC: 124 AN: 290

European-Non Finnish (NFE) AF: 0.499 AC: 33765 AN: 67718

Other (OTH) AF: 0.516 AC: 1080 AN: 2092

Alfa AF: 0.493 Hom.: 68586

Bravo AF: 0.492

Asia WGS AF: 0.520 AC: 1807 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.0
DANN	Benign	0.37
PhyloP100		0.61
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: rs10010325; hg19: chr4-106106353;