10-68618234-T-C

Variant summary

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

The NM_030625.3(TET1):c.1968+17200T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,064 control chromosomes in the GnomAD database, including 5,760 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 0.27 (5760 hom., cov: 32)
• Consequence: TET1 NM_030625.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.686

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TET1	NM_030625.3	c.1968+17200T>C		intron_variant		ENST00000373644.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TET1	ENST00000373644.5	c.1968+17200T>C		intron_variant		1	NM_030625.3	P1

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40398 AN: 151946 Hom.: 5747 Cov.: 32

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.251

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

GnomAD4 genome AF: 0.266 AC: 40454 AN: 152064 Hom.: 5760 Cov.: 32 AF XY: 0.268 AC XY: 19899 AN XY: 74322

Gnomad4 AFR AF: 0.351

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.172

Gnomad4 SAS AF: 0.320

Gnomad4 FIN AF: 0.262

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.253

Alfa AF: 0.215 Hom.: 2055

Bravo AF: 0.269

Asia WGS AF: 0.278 AC: 966 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	2.1
Dann	Benign	0.49

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: rs2664420; hg19: chr10-70377991;