4-105207603-G-A

Variant names:

• chr4-105207603-G-A
• rs1391441
• NM_001127208.3:c.-47+17098G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001127208.3(TET2):​c.-47+17098G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.696 in 151,752 control chromosomes in the GnomAD database, including 37,554 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 0.70 (37554 hom., cov: 30)
• Consequence: TET2 NM_001127208.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• Publications: 10 publications found

Genes affected

TET2 (HGNC:25941): (tet methylcytosine dioxygenase 2) The protein encoded by this gene is a methylcytosine dioxygenase that catalyzes the conversion of methylcytosine to 5-hydroxymethylcytosine. The encoded protein is involved in myelopoiesis, and defects in this gene have been associated with several myeloproliferative disorders. Two variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2011]

TET2-AS1 (HGNC:41125): (TET2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127208.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TET2	NM_001127208.3	MANE Select	c.-47+17098G>A		intron	N/A	NP_001120680.1
	TET2	NM_017628.4		c.-47+17098G>A		intron	N/A	NP_060098.3
	TET2-AS1	NR_126420.1		n.319-29931C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TET2	ENST00000380013.9	TSL:5 MANE Select	c.-47+17098G>A		intron	N/A	ENSP00000369351.4
	TET2	ENST00000513237.5	TSL:1	c.17+17117G>A		intron	N/A	ENSP00000425443.1
	TET2	ENST00000540549.5	TSL:1	c.-47+17117G>A		intron	N/A	ENSP00000442788.1

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105534 AN: 151632 Hom.: 37509 Cov.: 30

Gnomad AFR AF: 0.846

Gnomad AMI AF: 0.698

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.662

Gnomad OTH AF: 0.672

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

GnomAD4 genome AF: 0.696 AC: 105628 AN: 151752 Hom.: 37554 Cov.: 30 AF XY: 0.688 AC XY: 50972 AN XY: 74124

African (AFR) AF: 0.846 AC: 35043 AN: 41430

American (AMR) AF: 0.627 AC: 9546 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.590 AC: 2041 AN: 3460

East Asian (EAS) AF: 0.473 AC: 2427 AN: 5136

South Asian (SAS) AF: 0.582 AC: 2804 AN: 4820

European-Finnish (FIN) AF: 0.633 AC: 6635 AN: 10490

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.662 AC: 44927 AN: 67894

Other (OTH) AF: 0.663 AC: 1394 AN: 2102

Alfa AF: 0.666 Hom.: 28515

Bravo AF: 0.704

Asia WGS AF: 0.552 AC: 1923 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.10
DANN	Benign	0.37
PhyloP100		-1.3
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: rs1391441; hg19: chr4-106128760;