10-68650873-C-T

Variant names:

• chr10-68650873-C-T
• rs7913568
• NM_030625.3:c.4277-973C>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.4277-973C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.722 in 151,992 control chromosomes in the GnomAD database, including 41,159 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 0.72 (41159 hom., cov: 31)
• Consequence: TET1 NM_030625.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 5 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030625.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TET1	NM_030625.3	MANE Select	c.4277-973C>T		intron	N/A	NP_085128.2	Q8NFU7-1
	TET1	NM_001406365.1		c.4277-973C>T		intron	N/A	NP_001393294.1
	TET1	NM_001406367.1		c.2366-973C>T		intron	N/A	NP_001393296.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TET1	ENST00000373644.5	TSL:1 MANE Select	c.4277-973C>T		intron	N/A	ENSP00000362748.4	Q8NFU7-1
	TET1	ENST00000929765.1		c.4379-973C>T		intron	N/A	ENSP00000599824.1
	TET1	ENST00000929763.1		c.4277-973C>T		intron	N/A	ENSP00000599822.1

Frequencies

GnomAD3 genomes AF: 0.722 AC: 109696 AN: 151874 Hom.: 41157 Cov.: 31

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.910

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.896

Gnomad EAS AF: 0.839

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.797

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.818

Gnomad OTH AF: 0.763

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

GnomAD4 genome AF: 0.722 AC: 109734 AN: 151992 Hom.: 41159 Cov.: 31 AF XY: 0.723 AC XY: 53682 AN XY: 74300

African (AFR) AF: 0.497 AC: 20587 AN: 41406

American (AMR) AF: 0.756 AC: 11543 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.896 AC: 3112 AN: 3472

East Asian (EAS) AF: 0.838 AC: 4332 AN: 5168

South Asian (SAS) AF: 0.724 AC: 3484 AN: 4814

European-Finnish (FIN) AF: 0.797 AC: 8405 AN: 10552

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.818 AC: 55596 AN: 67994

Other (OTH) AF: 0.762 AC: 1609 AN: 2112

Alfa AF: 0.782 Hom.: 124368

Bravo AF: 0.712

Asia WGS AF: 0.727 AC: 2526 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.42
DANN	Benign	0.62
PhyloP100		-1.1
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: rs7913568; hg19: chr10-70410630;