chr17-31304814-G-C

Variant names:

• chr17-31304814-G-C
• rs112236394
• NM_006495.4:c.796C>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006495.4(EVI2B):​c.796C>G​(p.Arg266Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EVI2B NM_006495.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.12

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.784

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EVI2B	NM_006495.4	c.796C>G	p.Arg266Gly	missense_variant	Exon 2 of 2	ENST00000330927.5	NP_006486.3
NF1	NM_001042492.3	c.4836-21006G>C		intron_variant	Intron 36 of 57	ENST00000358273.9	NP_001035957.1
NF1	NM_000267.3	c.4773-21006G>C		intron_variant	Intron 35 of 56		NP_000258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EVI2B	ENST00000330927.5	c.796C>G	p.Arg266Gly	missense_variant	Exon 2 of 2	1	NM_006495.4	ENSP00000333779.4
NF1	ENST00000358273.9	c.4836-21006G>C		intron_variant	Intron 36 of 57	1	NM_001042492.3	ENSP00000351015.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.10
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T;T
Eigen	Benign	0.17
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.52	.;T
M_CAP	Benign	0.038	D
MetaRNN	Pathogenic	0.78	D;D
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	2.0	M;M
PrimateAI	Benign	0.27	T
PROVEAN	Pathogenic	-5.7	D;.
REVEL	Benign	0.28
Sift	Uncertain	0.012	D;.
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.93	P;P
Vest4		0.74
MVP		0.80
MPC		0.043
ClinPred		0.92	D
GERP RS		4.5
Varity_R		0.29
gMVP		0.43

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

Other links and lift over

dbSNP: rs112236394; hg19: chr17-29631832;