7-13895918-G-A

Position:

chr7-13895918-G-A

Variant summary

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

The NM_004956.5(ETV1):c.1382C>T(p.Pro461Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000031 in 1,613,434 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: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

ETV1
NM_004956.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.79

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 made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.096853554).

BS2

High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ETV1	NM_004956.5 link	c.1382C>T	p.Pro461Leu	missense_variant	14/14	ENST00000430479.6	NP_004947.2	P50549-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ETV1	ENST00000430479.6 link	c.1382C>T	p.Pro461Leu	missense_variant	14/14	1	NM_004956.5	ENSP00000405327.1	P50549-1
ETV1	ENST00000405358.8 link	c.1424C>T	p.Pro475Leu	missense_variant	12/12	5		ENSP00000384085.4	B5MCT2
ETV1	ENST00000405218.6 link	c.1382C>T	p.Pro461Leu	missense_variant	13/13	5		ENSP00000385551.2	P50549-1
ETV1	ENST00000403685.5 link	c.1328C>T	p.Pro443Leu	missense_variant	12/12	1		ENSP00000385686.1	P50549-2
ETV1	ENST00000403527.6 link	c.1262C>T	p.Pro421Leu	missense_variant	10/10	1		ENSP00000384138.1	P50549-6
ETV1	ENST00000438956.6 link	c.1208C>T	p.Pro403Leu	missense_variant	9/9	1		ENSP00000393078.2	P50549-5C9JX69
ETV1	ENST00000443137.5 link	n.*342C>T		non_coding_transcript_exon_variant	15/15	2		ENSP00000413836.1	F8WEH6
ETV1	ENST00000443137.5 link	n.*342C>T		3_prime_UTR_variant	15/15	2		ENSP00000413836.1	F8WEH6

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

248410

Hom.:

AF XY:

0.00000742

AC XY:

AN XY:

134734

show subpopulations

Gnomad AFR exome

AF:

0.0000648

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:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000308

AC:

AN:

1461270

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

726882

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.0000351

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152164

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000165

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

Oct 04, 2022

The c.1382C>T (p.P461L) alteration is located in exon 14 (coding exon 12) of the ETV1 gene. This alteration results from a C to T substitution at nucleotide position 1382, causing the proline (P) at amino acid position 461 to be replaced by a leucine (L). 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

0.099

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.46

CADD

Uncertain

DANN

Benign

0.72

DEOGEN2

Uncertain

0.47

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

Eigen

Benign

-0.12

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.94

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

M_CAP

Benign

0.0095

MetaRNN

Benign

0.097

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

MetaSVM

Benign

-0.85

MutationAssessor

Benign

-0.23

N;.;.;.;.;.;.;N;.

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-3.5

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

REVEL

Benign

0.12

Sift

Benign

0.63

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

Sift4G

Benign

0.54

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

Polyphen

0.0

B;.;.;B;.;P;.;B;B

Vest4

0.25

MutPred

0.35

.;.;.;.;.;Loss of disorder (P = 0.0179);.;.;.;

MVP

0.14

MPC

0.15

ClinPred

0.13

GERP RS

4.5

Varity_R

0.17

gMVP

0.53

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