7-13931589-T-C

Position:

chr7-13931589-T-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_004956.5(ETV1):c.715A>G(p.Asn239Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000397 in 1,613,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

ETV1
NM_004956.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.71

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:

ETV1 (HGNC:):

ETV1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10990319).

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ETV1	NM_004956.5 linkuse as main transcript	c.715A>G	p.Asn239Asp	missense_variant	9/14	ENST00000430479.6	NP_004947.2	P50549-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ETV1	ENST00000430479.6 linkuse as main transcript	c.715A>G	p.Asn239Asp	missense_variant	9/14	1	NM_004956.5	ENSP00000405327.1	P50549-1
ETV1	ENST00000405358.8 linkuse as main transcript	c.757A>G	p.Asn253Asp	missense_variant	7/12	5		ENSP00000384085.4	B5MCT2
ETV1	ENST00000405218.6 linkuse as main transcript	c.715A>G	p.Asn239Asp	missense_variant	8/13	5		ENSP00000385551.2	P50549-1
ETV1	ENST00000403685.5 linkuse as main transcript	c.661A>G	p.Asn221Asp	missense_variant	7/12	1		ENSP00000385686.1	P50549-2
ETV1	ENST00000403527.6 linkuse as main transcript	c.595A>G	p.Asn199Asp	missense_variant	5/10	1		ENSP00000384138.1	P50549-6
ETV1	ENST00000438956.6 linkuse as main transcript	c.541A>G	p.Asn181Asp	missense_variant	4/9	1		ENSP00000393078.2	P50549-5C9JX69
ETV1	ENST00000443137.5 linkuse as main transcript	n.715A>G		non_coding_transcript_exon_variant	9/15	2		ENSP00000413836.1	F8WEH6

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000140

AC:

AN:

249262

Hom.:

AF XY:

0.000140

AC XY:

AN XY:

135232

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000608

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000885

Gnomad OTH exome

AF:

0.000661

GnomAD4 exome

AF:

0.0000397

AC:

AN:

1461712

Hom.:

Cov.:

AF XY:

0.0000413

AC XY:

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000537

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000297

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152250

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000450

Hom.:

Bravo

AF:

0.000155

ExAC

AF:

0.0000744

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 13, 2021

The c.715A>G (p.N239D) alteration is located in exon 9 (coding exon 7) of the ETV1 gene. This alteration results from a A to G substitution at nucleotide position 715, causing the asparagine (N) at amino acid position 239 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.064

T;.;.;.;.;.;.;T;.;.;.

Eigen

Benign

0.027

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.92

.;D;D;D;D;D;D;D;.;D;D

M_CAP

Benign

0.0049

MetaRNN

Benign

0.11

T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;.;.;.;L;.;.;L;.;.;.

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.35

N;N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.064

Sift

Benign

0.23

T;T;T;T;T;T;T;T;T;T;T

Sift4G

Benign

0.60

T;T;T;T;T;T;T;T;T;.;T

Polyphen

0.011

B;.;.;B;.;B;.;B;B;.;.

Vest4

0.50

MutPred

0.45

.;.;.;.;.;Gain of glycosylation at S258 (P = 0.1254);.;.;.;.;.;

MVP

0.30

MPC

0.19

ClinPred

0.039

GERP RS

6.1

Varity_R

0.086

gMVP

0.11

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over