chr17-31304852-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_006495.4(EVI2B):c.758G>T(p.Cys253Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000359 in 1,614,020 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0019 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 1 hom. )

Consequence

EVI2B
NM_006495.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.237

Publications

4 publications found

Variant links:

Genes affected

EVI2B (HGNC:3500): (ecotropic viral integration site 2B) Involved in positive regulation of granulocyte differentiation. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

EVI2B 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 Gene-Disease associations (from GenCC):

neurofibromatosis type 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia, G2P, Genomics England PanelApp
neurofibromatosis-Noonan syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, PanelApp Australia
Moyamoya disease
Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
hereditary pheochromocytoma-paraganglioma
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
familial ovarian cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

NF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004789889).

BP6

Variant 17-31304852-C-A is Benign according to our data. Variant chr17-31304852-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 446081.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EVI2B	NM_006495.4 link	c.758G>T	p.Cys253Phe	missense_variant	Exon 2 of 2	ENST00000330927.5	NP_006486.3	P34910-1Q9BRW1
NF1	NM_001042492.3 link	c.4836-20968C>A		intron_variant	Intron 36 of 57	ENST00000358273.9	NP_001035957.1	P21359-1
NF1	NM_000267.4 link	c.4773-20968C>A		intron_variant	Intron 35 of 56		NP_000258.1	P21359-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EVI2B	ENST00000330927.5 link	c.758G>T	p.Cys253Phe	missense_variant	Exon 2 of 2	1	NM_006495.4	ENSP00000333779.4		P34910-1
NF1	ENST00000358273.9 link	c.4836-20968C>A		intron_variant	Intron 36 of 57	1	NM_001042492.3	ENSP00000351015.4		P21359-1

Frequencies

GnomAD3 genomes

AF:

0.00191

AC:

290

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00672

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

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:

0.0000147

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.000451

AC:

113

AN:

250736

AF XY:

0.000347

show subpopulations

Gnomad AFR exome

AF:

0.00605

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.000328

GnomAD4 exome

AF:

0.000198

AC:

289

AN:

1461770

Hom.:

Cov.:

AF XY:

0.000173

AC XY:

126

AN XY:

727184

show subpopulations

African (AFR)

AF:

0.00684

AC:

229

AN:

33478

American (AMR)

AF:

0.000335

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39682

South Asian (SAS)

AF:

0.00

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53358

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000189

AC:

AN:

1111990

Other (OTH)

AF:

0.000397

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00191

AC:

291

AN:

152250

Hom.:

Cov.:

AF XY:

0.00191

AC XY:

142

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.00672

AC:

279

AN:

41516

American (AMR)

AF:

0.000523

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68022

Other (OTH)

AF:

0.00142

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000624

Hom.:

Bravo

AF:

0.00206

ESP6500AA

AF:

0.00613

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000585

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 03, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 27, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.095

T;T

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.42

.;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.0048

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;L

PhyloP100

-0.24

PrimateAI

Benign

0.46

PROVEAN

Pathogenic

-5.5

D;.

REVEL

Benign

0.040

Sift

Benign

0.24

T;.

Sift4G

Benign

0.88

T;T

Polyphen

0.21

B;B

Vest4

0.090

MVP

0.26

MPC

0.28

ClinPred

0.056

GERP RS

1.2

Varity_R

0.16

gMVP

0.081

Mutation Taster

=98/2

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over