dbSNP rs10491990: ETV6:c.163+34015G>A (chr12-11786594-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001987.5(ETV6):c.163+34015G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,192 control chromosomes in the GnomAD database, including 1,878 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 0.13 ( 1878 hom., cov: 32)

Consequence

ETV6
NM_001987.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0610

Publications

3 publications found

Variant links:

Genes affected

ETV6 (HGNC:3495): (ETS variant transcription factor 6) This gene encodes an ETS family transcription factor. The product of this gene contains two functional domains: a N-terminal pointed (PNT) domain that is involved in protein-protein interactions with itself and other proteins, and a C-terminal DNA-binding domain. Gene knockout studies in mice suggest that it is required for hematopoiesis and maintenance of the developing vascular network. This gene is known to be involved in a large number of chromosomal rearrangements associated with leukemia and congenital fibrosarcoma. [provided by RefSeq, Sep 2008]

ETV6 Gene-Disease associations (from GenCC):

thrombocytopenia 5
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, ClinGen, PanelApp Australia, Labcorp Genetics (formerly Invitae)
acute myeloid leukemia
Inheritance: AD, Unknown Classification: STRONG, LIMITED Submitted by: Genomics England PanelApp, Ambry Genetics
hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ETV6 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001987.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001987.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ETV6	NM_001987.5	MANE Select	c.163+34015G>A	intron	N/A	NP_001978.1	P41212
ETV6	NM_001413913.1		c.160+34015G>A	intron	N/A	NP_001400842.1
ETV6	NM_001413914.1		c.136+34015G>A	intron	N/A	NP_001400843.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ETV6	ENST00000396373.9	TSL:1 MANE Select	c.163+34015G>A	intron	N/A	ENSP00000379658.3	P41212
ETV6	ENST00000904922.1		c.160+34015G>A	intron	N/A	ENSP00000574981.1
ETV6	ENST00000904923.1		c.163+34015G>A	intron	N/A	ENSP00000574982.1

Frequencies

GnomAD3 genomes

AF:

0.131

AC:

19994

AN:

152074

Hom.:

1879

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0398

Gnomad AMI

AF:

0.0592

Gnomad AMR

AF:

0.0860

Gnomad ASJ

AF:

0.151

Gnomad EAS

AF:

0.399

Gnomad SAS

AF:

0.304

Gnomad FIN

AF:

0.211

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.152

Gnomad OTH

AF:

0.140

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

GnomAD4 genome

AF:

0.131

AC:

20001

AN:

152192

Hom.:

1878

Cov.:

AF XY:

0.140

AC XY:

10382

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.0399

AC:

1657

AN:

41532

American (AMR)

AF:

0.0860

AC:

1314

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.151

AC:

523

AN:

3472

East Asian (EAS)

AF:

0.400

AC:

2067

AN:

5168

South Asian (SAS)

AF:

0.304

AC:

1471

AN:

4832

European-Finnish (FIN)

AF:

0.211

AC:

2229

AN:

10582

Middle Eastern (MID)

AF:

0.126

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.152

AC:

10350

AN:

68002

Other (OTH)

AF:

0.141

AC:

299

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

840

1681

2521

3362

4202

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

234

468

702

936

1170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.132

Hom.:

1368

Bravo

AF:

0.115

Asia WGS

AF:

0.311

AC:

1080

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

3.3

(source)

DANN

Benign

0.77

PhyloP100

-0.061

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over