rs17884293

Positions:

• chr17-31304591-G-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_006495.4(EVI2B):​c.1019C>G​(p.Pro340Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000363 in 1,614,132 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00020 (2 hom.)
• Consequence: EVI2B NM_006495.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.24

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]

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009092718).
• BP6: Variant 17-31304591-G-C is Benign according to our data. Variant chr17-31304591-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 235483.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-31304591-G-C is described in Lovd as [Benign].
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EVI2B	NM_006495.4	c.1019C>G	p.Pro340Arg	missense_variant	2/2	ENST00000330927.5	NP_006486.3
NF1	NM_001042492.3	c.4836-21229G>C		intron_variant		ENST00000358273.9	NP_001035957.1
NF1	NM_000267.3	c.4773-21229G>C		intron_variant			NP_000258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EVI2B	ENST00000330927.5	c.1019C>G	p.Pro340Arg	missense_variant	2/2	1	NM_006495.4	ENSP00000333779.4
NF1	ENST00000358273.9	c.4836-21229G>C		intron_variant		1	NM_001042492.3	ENSP00000351015.4

Frequencies

GnomAD3 genomes AF: 0.00195 AC: 297 AN: 152156 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00681

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

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: 0.00

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.000534 AC: 134 AN: 251164 Hom.: 0 AF XY: 0.000435 AC XY: 59 AN XY: 135726

Gnomad AFR exome AF: 0.00738

Gnomad AMR exome AF: 0.000318

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: 0.0000176

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000198 AC: 289 AN: 1461858 Hom.: 2 Cov.: 32 AF XY: 0.000176 AC XY: 128 AN XY: 727232

Gnomad4 AFR exome AF: 0.00735

Gnomad4 AMR exome AF: 0.000358

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.000381

GnomAD4 genome AF: 0.00195 AC: 297 AN: 152274 Hom.: 0 Cov.: 32 AF XY: 0.00199 AC XY: 148 AN XY: 74462

Gnomad4 AFR AF: 0.00679

Gnomad4 AMR AF: 0.000719

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000376 Hom.: 0

Bravo AF: 0.00242

ESP6500AA AF: 0.00726 AC: 32

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000651 AC: 79

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Neurofibromatosis, type 1 Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Mar 15, 2022	- -
Likely benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

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

Jan 11, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;T
Eigen	Benign	0.081
Eigen_PC	Benign	-0.0012
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.51	.;T
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.0091	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.8	L;L
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-3.7	D;.
REVEL	Benign	0.20
Sift	Benign	0.068	T;.
Sift4G	Benign	0.095	T;T
Polyphen		1.0	D;D
Vest4		0.34
MVP		0.68
MPC		0.26
ClinPred		0.039	T
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.12
gMVP		0.066

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs17884293; hg19: chr17-29631609;