rs1129506

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001003927.3(EVI2A):c.69C>T(p.Ser23Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 1,589,844 control chromosomes in the GnomAD database, including 307,676 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.64 ( 31363 hom., cov: 31)

Exomes 𝑓: 0.62 ( 276313 hom. )

Consequence

EVI2A
NM_001003927.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0580

Variant links:

Genes affected

EVI2A (HGNC:3499): (ecotropic viral integration site 2A) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

EVI2A links:

NF1 (HGNC:7765): (neurofibromin 1) This gene product appears to function as a negative regulator of the ras signal transduction pathway. Mutations in this gene have been linked to neurofibromatosis type 1, juvenile myelomonocytic leukemia and Watson syndrome. The mRNA for this gene is subject to RNA editing (CGA>UGA->Arg1306Term) resulting in premature translation termination. Alternatively spliced transcript variants encoding different isoforms have also been described for this gene. [provided by RefSeq, Jul 2008]

NF1 links:

ENSG00000265118 (HGNC:):

ENSG00000265118 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 17-31319014-G-A is Benign according to our data. Variant chr17-31319014-G-A is described in ClinVar as [Benign]. Clinvar id is 403230.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.058 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EVI2A	NM_014210.4 link	c.-1C>T		5_prime_UTR_variant	Exon 2 of 2	ENST00000462804.3	NP_055025.2	P22794-1
NF1	NM_001042492.3 link	c.4836-6806G>A		intron_variant	Intron 36 of 57	ENST00000358273.9	NP_001035957.1	P21359-1
EVI2A	NM_001003927.3 link	c.69C>T	p.Ser23Ser	synonymous_variant	Exon 3 of 3		NP_001003927.1	P22794-2
NF1	NM_000267.3 link	c.4773-6806G>A		intron_variant	Intron 35 of 56		NP_000258.1	P21359-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
EVI2A	ENST00000462804.3 link	c.-1C>T	5_prime_UTR_variant	Exon 2 of 2	1	NM_014210.4	ENSP00000420557.3	P22794-1
NF1	ENST00000358273.9 link	c.4836-6806G>A	intron_variant	Intron 36 of 57	1	NM_001042492.3	ENSP00000351015.4	P21359-1
ENSG00000265118	ENST00000578584.5 link	c.-229C>T	upstream_gene_variant		2		ENSP00000463981.2	J3QR06

Frequencies

GnomAD3 genomes

AF:

0.638

AC:

96842

AN:

151904

Hom.:

31336

Cov.:

show subpopulations

Gnomad AFR

AF:

0.716

Gnomad AMI

AF:

0.696

Gnomad AMR

AF:

0.508

Gnomad ASJ

AF:

0.702

Gnomad EAS

AF:

0.445

Gnomad SAS

AF:

0.620

Gnomad FIN

AF:

0.620

Gnomad MID

AF:

0.669

Gnomad NFE

AF:

0.633

Gnomad OTH

AF:

0.645

GnomAD3 exomes

AF:

0.590

AC:

136600

AN:

231562

Hom.:

41384

AF XY:

0.599

AC XY:

75396

AN XY:

125804

show subpopulations

Gnomad AFR exome

AF:

0.717

Gnomad AMR exome

AF:

0.415

Gnomad ASJ exome

AF:

0.702

Gnomad EAS exome

AF:

0.437

Gnomad SAS exome

AF:

0.623

Gnomad FIN exome

AF:

0.614

Gnomad NFE exome

AF:

0.624

Gnomad OTH exome

AF:

0.605

GnomAD4 exome

AF:

0.617

AC:

887360

AN:

1437822

Hom.:

276313

Cov.:

AF XY:

0.619

AC XY:

441941

AN XY:

714530

show subpopulations

Gnomad4 AFR exome

AF:

0.725

Gnomad4 AMR exome

AF:

0.425

Gnomad4 ASJ exome

AF:

0.703

Gnomad4 EAS exome

AF:

0.470

Gnomad4 SAS exome

AF:

0.627

Gnomad4 FIN exome

AF:

0.610

Gnomad4 NFE exome

AF:

0.623

Gnomad4 OTH exome

AF:

0.620

GnomAD4 genome

AF:

0.637

AC:

96905

AN:

152022

Hom.:

31363

Cov.:

AF XY:

0.633

AC XY:

47016

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.716

Gnomad4 AMR

AF:

0.507

Gnomad4 ASJ

AF:

0.702

Gnomad4 EAS

AF:

0.444

Gnomad4 SAS

AF:

0.618

Gnomad4 FIN

AF:

0.620

Gnomad4 NFE

AF:

0.633

Gnomad4 OTH

AF:

0.641

Alfa

AF:

0.624

Hom.:

49154

Bravo

AF:

0.632

Asia WGS

AF:

0.523

AC:

1818

AN:

3478

EpiCase

AF:

0.644

EpiControl

AF:

0.636

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

EVI2A-related disorder

Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.2

DANN

Benign

0.51

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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