7-13911249-G-T

Position:

chr7-13911249-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004956.5(ETV1):c.861C>A(p.Ser287Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,774 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: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ETV1
NM_004956.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.00

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ETV1	NM_004956.5 linkuse as main transcript	c.861C>A	p.Ser287Arg	missense_variant	10/14	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.861C>A	p.Ser287Arg	missense_variant	10/14	1	NM_004956.5	ENSP00000405327.1	P50549-1
ETV1	ENST00000405358.8 linkuse as main transcript	c.903C>A	p.Ser301Arg	missense_variant	8/12	5		ENSP00000384085.4	B5MCT2
ETV1	ENST00000405218.6 linkuse as main transcript	c.861C>A	p.Ser287Arg	missense_variant	9/13	5		ENSP00000385551.2	P50549-1
ETV1	ENST00000403685.5 linkuse as main transcript	c.807C>A	p.Ser269Arg	missense_variant	8/12	1		ENSP00000385686.1	P50549-2
ETV1	ENST00000403527.6 linkuse as main transcript	c.741C>A	p.Ser247Arg	missense_variant	6/10	1		ENSP00000384138.1	P50549-6
ETV1	ENST00000438956.6 linkuse as main transcript	c.687C>A	p.Ser229Arg	missense_variant	5/9	1		ENSP00000393078.2	P50549-5C9JX69
ETV1	ENST00000443137.5 linkuse as main transcript	n.861C>A		non_coding_transcript_exon_variant	10/15	2		ENSP00000413836.1	F8WEH6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248790

Hom.:

AF XY:

0.00000741

AC XY:

AN XY:

134944

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000886

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459774

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726276

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000828

AC:

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

May 23, 2023

The c.861C>A (p.S287R) alteration is located in exon 10 (coding exon 8) of the ETV1 gene. This alteration results from a C to A substitution at nucleotide position 861, causing the serine (S) at amino acid position 287 to be replaced by an arginine (R). 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

Uncertain

0.47

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

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

Eigen

Benign

0.050

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.96

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

M_CAP

Benign

0.0065

MetaRNN

Benign

0.29

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

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

PROVEAN

Benign

-2.1

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

REVEL

Benign

0.093

Sift

Uncertain

0.015

D;D;D;D;D;D;D;D;D

Sift4G

Benign

0.43

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

Polyphen

0.039, 0.17

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

Vest4

0.49

MutPred

0.54

.;.;.;.;Loss of phosphorylation at S301 (P = 0.0445);.;.;.;.;

MVP

0.31

MPC

0.20

ClinPred

0.53

GERP RS

5.3

Varity_R

0.25

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.23

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.23

Position offset: -37

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