Variant 3-186080022-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004454.3(ETV5):c.445C>G(p.Leu149Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00218 in 1,547,248 control chromosomes in the GnomAD database, including 75 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 31 hom., cov: 31)

Exomes 𝑓: 0.0011 ( 44 hom. )

Consequence

ETV5
NM_004454.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.03

Variant links:

Genes affected

ETV5 (HGNC:3494): (ETS variant transcription factor 5) Enables DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Involved in cellular response to oxidative stress; negative regulation of transcription by RNA polymerase II; and positive regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ETV5 links:

ETV5-AS1 (HGNC:):

ETV5-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027337074).

BP6

Variant 3-186080022-G-C is Benign according to our data. Variant chr3-186080022-G-C is described in ClinVar as [Benign]. Clinvar id is 780903.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0122 (1848/152070) while in subpopulation AFR AF= 0.0423 (1753/41398). AF 95% confidence interval is 0.0407. There are 31 homozygotes in gnomad4. There are 894 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1848 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ETV5	NM_004454.3 linkuse as main transcript	c.445C>G	p.Leu149Val	missense_variant	7/13	ENST00000306376.10	NP_004445.1	P41161-1
ETV5-AS1	NR_046594.1 linkuse as main transcript	n.173-538G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ETV5	ENST00000306376.10 linkuse as main transcript	c.445C>G	p.Leu149Val	missense_variant	7/13	1	NM_004454.3	ENSP00000306894.5		P41161-1

Frequencies

GnomAD3 genomes

AF:

0.0122

AC:

1851

AN:

151952

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0425

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00445

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00958

GnomAD3 exomes

AF:

0.00281

AC:

536

AN:

190758

Hom.:

AF XY:

0.00210

AC XY:

221

AN XY:

105412

show subpopulations

Gnomad AFR exome

AF:

0.0401

Gnomad AMR exome

AF:

0.00195

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000902

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000433

Gnomad OTH exome

AF:

0.000683

GnomAD4 exome

AF:

0.00110

AC:

1532

AN:

1395178

Hom.:

Cov.:

AF XY:

0.000944

AC XY:

653

AN XY:

691436

show subpopulations

Gnomad4 AFR exome

AF:

0.0428

Gnomad4 AMR exome

AF:

0.00260

Gnomad4 ASJ exome

AF:

0.0000421

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000110

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000239

Gnomad4 OTH exome

AF:

0.00284

GnomAD4 genome

AF:

0.0122

AC:

1848

AN:

152070

Hom.:

Cov.:

AF XY:

0.0120

AC XY:

894

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0423

Gnomad4 AMR

AF:

0.00445

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00948

Alfa

AF:

0.00386

Hom.:

Bravo

AF:

0.0143

ESP6500AA

AF:

0.0379

AC:

165

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00400

AC:

485

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 14, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.057

T;T;T

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.093

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.60

.;T;T

MetaRNN

Benign

0.0027

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N;.

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.27

N;N;N

REVEL

Benign

0.060

Sift

Benign

0.16

T;T;D

Sift4G

Benign

1.0

T;T;D

Polyphen

0.0010

B;B;.

Vest4

0.12

MVP

0.40

MPC

0.24

ClinPred

0.0017

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.072

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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