rs10762236

chr10-68671663-G-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
TET1	NM_030625.3	c.4674-1232G>T		intron_variant		ENST00000373644.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TET1	ENST00000373644.5	c.4674-1232G>T		intron_variant		1	NM_030625.3	P1

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

Gnomad4 AFR AF: 0.540

Gnomad4 AMR AF: 0.748

Gnomad4 ASJ AF: 0.890

Gnomad4 EAS AF: 0.835

Gnomad4 SAS AF: 0.751

Gnomad4 FIN AF: 0.794

Gnomad4 NFE AF: 0.823

Gnomad4 OTH AF: 0.765

Alfa AF: 0.811 Hom.: 44271

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

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: rs10762236; hg19: chr10-70431420;