rs16925584

chr10-68660165-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030625.3(TET1):c.4462-6880G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 151,960 control chromosomes in the GnomAD database, including 3,147 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 0.18 (3147 hom., cov: 32)
• Consequence: TET1 NM_030625.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TET1	NM_030625.3	c.4462-6880G>A		intron_variant		ENST00000373644.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TET1	ENST00000373644.5	c.4462-6880G>A		intron_variant		1	NM_030625.3	P1

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27658 AN: 151842 Hom.: 3138 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.0591

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.182 AC: 27694 AN: 151960 Hom.: 3147 Cov.: 32 AF XY: 0.184 AC XY: 13653 AN XY: 74266

Gnomad4 AFR AF: 0.313

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.0591

Gnomad4 EAS AF: 0.137

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.146

Alfa AF: 0.174 Hom.: 348

Bravo AF: 0.185

Asia WGS AF: 0.185 AC: 644 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	1.9
Dann	Benign	0.36

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: rs16925584; hg19: chr10-70419922;