7-13895912-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_004956.5(ETV1):c.1388G>A(p.Gly463Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,462 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ETV1
NM_004956.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.00

Publications

2 publications found

Variant links:

COSMIC-nc: COSV54136357

Genes affected

ETV1 (HGNC:3490): (ETS variant transcription factor 1) This gene encodes a member of the ETS (E twenty-six) family of transcription factors. The ETS proteins regulate many target genes that modulate biological processes like cell growth, angiogenesis, migration, proliferation and differentiation. All ETS proteins contain an ETS DNA-binding domain that binds to DNA sequences containing the consensus 5'-CGGA[AT]-3'. The protein encoded by this gene contains a conserved short acidic transactivation domain (TAD) in the N-terminal region, in addition to the ETS DNA-binding domain in the C-terminal region. This gene is involved in chromosomal translocations, which result in multiple fusion proteins including EWS-ETV1 in Ewing sarcoma and at least 10 ETV1 partners (see PMID: 19657377, Table 1) in prostate cancer. In addition to chromosomal rearrangement, this gene is overexpressed in prostate cancer, melanoma and gastrointestinal stromal tumor. Multiple alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2016]

ETV1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35551292).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004956.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ETV1	NM_004956.5	MANE Select	c.1388G>A	p.Gly463Glu	missense	Exon 14 of 14	NP_004947.2
ETV1	NM_001370555.1		c.1388G>A	p.Gly463Glu	missense	Exon 13 of 13	NP_001357484.1	P50549-1
ETV1	NM_001370556.1		c.1340G>A	p.Gly447Glu	missense	Exon 12 of 12	NP_001357485.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ETV1	ENST00000430479.6	TSL:1 MANE Select	c.1388G>A	p.Gly463Glu	missense	Exon 14 of 14	ENSP00000405327.1	P50549-1
ETV1	ENST00000405358.8	TSL:5	c.1430G>A	p.Gly477Glu	missense	Exon 12 of 12	ENSP00000384085.4	B5MCT2
ETV1	ENST00000405218.6	TSL:5	c.1388G>A	p.Gly463Glu	missense	Exon 13 of 13	ENSP00000385551.2	P50549-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

248622

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461462

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726966

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86170

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53384

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111806

Other (OTH)

AF:

0.00

AC:

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.083

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.17

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.0076

MetaRNN

Benign

0.36

MetaSVM

Benign

-1.2

MutationAssessor

Benign

2.0

PhyloP100

4.0

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.7

REVEL

Benign

0.13

Sift

Benign

0.25

Sift4G

Benign

0.42

Polyphen

0.073

Vest4

0.59

MutPred

0.30

Gain of disorder (P = 0.0435)

MVP

0.20

MPC

0.35

ClinPred

0.53

GERP RS

5.5

Varity_R

0.23

gMVP

0.68

Mutation Taster

=23/77

disease causing

(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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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