rs10762231

Positions:

• chr10-68563357-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.-123+2615G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 152,132 control chromosomes in the GnomAD database, including 14,149 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 0.42 (14149 hom., cov: 33)
• Consequence: TET1 NM_030625.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.210

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=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TET1	NM_030625.3	c.-123+2615G>A		intron_variant		ENST00000373644.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TET1	ENST00000373644.5	c.-123+2615G>A		intron_variant		1	NM_030625.3	P1

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64401 AN: 152016 Hom.: 14134 Cov.: 33

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.424 AC: 64461 AN: 152132 Hom.: 14149 Cov.: 33 AF XY: 0.426 AC XY: 31711 AN XY: 74384

Gnomad4 AFR AF: 0.519

Gnomad4 AMR AF: 0.410

Gnomad4 ASJ AF: 0.270

Gnomad4 EAS AF: 0.429

Gnomad4 SAS AF: 0.346

Gnomad4 FIN AF: 0.481

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.375

Alfa AF: 0.382 Hom.: 6524

Bravo AF: 0.426

Asia WGS AF: 0.370 AC: 1290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.9
DANN	Benign	0.51

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: rs10762231; hg19: chr10-70323114;