rs10762236

Variant names:

• chr10-68671663-G-T
• rs10762236
• NM_030625.3:c.4674-1232G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030625.3(TET1):​c.4674-1232G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.735 in 152,234 control chromosomes in the GnomAD database, including 42,396 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 0.74 (42396 hom., cov: 35)
• Consequence: TET1 NM_030625.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74
• Publications: 4 publications found

Genes affected

TET1 (HGNC:29484): (tet methylcytosine dioxygenase 1) DNA methylation is an epigenetic mechanism that is important for controlling gene expression. The protein encoded by this gene is a demethylase that belongs to the TET (ten-eleven translocation) family. Members of the TET protein family play a role in the DNA methylation process and gene activation. [provided by RefSeq, Sep 2015]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TET1	NM_030625.3	c.4674-1232G>T		intron_variant	Intron 7 of 11	ENST00000373644.5	NP_085128.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TET1	ENST00000373644.5	c.4674-1232G>T		intron_variant	Intron 7 of 11	1	NM_030625.3	ENSP00000362748.4

Frequencies

GnomAD3 genomes AF: 0.736 AC: 111918 AN: 152116 Hom.: 42402 Cov.: 35

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.908

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.890

Gnomad EAS AF: 0.836

Gnomad SAS AF: 0.749

Gnomad FIN AF: 0.794

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.823

Gnomad OTH AF: 0.766

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

GnomAD4 genome AF: 0.735 AC: 111948 AN: 152234 Hom.: 42396 Cov.: 35 AF XY: 0.735 AC XY: 54724 AN XY: 74424

African (AFR) AF: 0.540 AC: 22397 AN: 41510

American (AMR) AF: 0.748 AC: 11445 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.890 AC: 3089 AN: 3472

East Asian (EAS) AF: 0.835 AC: 4333 AN: 5188

South Asian (SAS) AF: 0.751 AC: 3624 AN: 4828

European-Finnish (FIN) AF: 0.794 AC: 8410 AN: 10596

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.823 AC: 55962 AN: 68024

Other (OTH) AF: 0.765 AC: 1618 AN: 2116

Alfa AF: 0.808 Hom.: 52766

Bravo AF: 0.726

Asia WGS AF: 0.738 AC: 2568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	3.7
DANN	Benign	0.52
PhyloP100		1.7
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: rs10762236; hg19: chr10-70431420;