7-13900829-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP3BS2

The NM_004956.5(ETV1):c.1121G>A(p.Arg374His) variant causes a missense change. The variant allele was found at a frequency of 0.0000124 in 1,453,924 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

ETV1
NM_004956.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.05

Publications

1 publications found

Variant links:

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: Likely_benign. The variant received -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.758

BS2

High AC in GnomAdExome4 at 18 AD gene.

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.1121G>A	p.Arg374His	missense	Exon 13 of 14	NP_004947.2
ETV1	NM_001370555.1		c.1121G>A	p.Arg374His	missense	Exon 12 of 13	NP_001357484.1	P50549-1
ETV1	NM_001370556.1		c.1073G>A	p.Arg358His	missense	Exon 11 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.1121G>A	p.Arg374His	missense	Exon 13 of 14	ENSP00000405327.1	P50549-1
ETV1	ENST00000405358.8	TSL:5	c.1163G>A	p.Arg388His	missense	Exon 11 of 12	ENSP00000384085.4	B5MCT2
ETV1	ENST00000405218.6	TSL:5	c.1121G>A	p.Arg374His	missense	Exon 12 of 13	ENSP00000385551.2	P50549-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000128

AC:

AN:

235122

AF XY:

0.0000236

show subpopulations

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:

0.0000283

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000124

AC:

AN:

1453924

Hom.:

Cov.:

AF XY:

0.0000180

AC XY:

AN XY:

722504

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33400

American (AMR)

AF:

0.00

AC:

AN:

43752

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25934

East Asian (EAS)

AF:

0.00

AC:

AN:

39554

South Asian (SAS)

AF:

0.0000118

AC:

AN:

84668

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52752

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.0000135

AC:

AN:

1108028

Other (OTH)

AF:

0.0000166

AC:

AN:

60076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

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.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000166

AC:

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

Pathogenic

0.89

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

0.020

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.75

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.032

MetaRNN

Pathogenic

0.76

MetaSVM

Benign

-0.34

MutationAssessor

Benign

1.9

PhyloP100

5.0

PrimateAI

Pathogenic

0.90

PROVEAN

Uncertain

-3.0

REVEL

Uncertain

0.32

Sift

Uncertain

0.017

Sift4G

Uncertain

0.058

Polyphen

0.94

Vest4

0.74

MutPred

0.73

Loss of MoRF binding (P = 0.0154)

MVP

0.54

MPC

0.68

ClinPred

0.90

GERP RS

5.8

Varity_R

0.51

gMVP

0.76

Mutation Taster

=3/97

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