Genetic Variant NM_002499.4:c.103A>T (chr15-73052778-A-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002499.4(NEO1):c.103A>T(p.Arg35Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000305 in 1,164,090 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 29)

Exomes 𝑓: 0.00012 ( 2 hom. )

Consequence

NEO1
NM_002499.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00800

Publications

0 publications found

Variant links:

Genes affected

NEO1 (HGNC:7754): (neogenin 1) This gene encodes a cell surface protein that is a member of the immunoglobulin superfamily. The encoded protein consists of four N-terminal immunoglobulin-like domains, six fibronectin type III domains, a transmembrane domain and a C-terminal internal domain that shares homology with the tumor suppressor candidate gene DCC. This protein may be involved in cell growth and differentiation and in cell-cell adhesion. Defects in this gene are associated with cell proliferation in certain cancers. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2010]

NEO1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009049892).

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002499.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NEO1	NM_002499.4	MANE Select	c.103A>T	p.Arg35Trp	missense	Exon 1 of 29	NP_002490.2	Q92859-1
NEO1	NM_001419531.1		c.103A>T	p.Arg35Trp	missense	Exon 2 of 30	NP_001406460.1
NEO1	NM_001172624.2		c.103A>T	p.Arg35Trp	missense	Exon 2 of 29	NP_001166095.1	Q92859-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NEO1	ENST00000261908.11	TSL:1 MANE Select	c.103A>T	p.Arg35Trp	missense	Exon 1 of 29	ENSP00000261908.6	Q92859-1
NEO1	ENST00000558964.5	TSL:1	c.103A>T	p.Arg35Trp	missense	Exon 1 of 28	ENSP00000453200.1	Q92859-4
NEO1	ENST00000560262.5	TSL:1	c.103A>T	p.Arg35Trp	missense	Exon 1 of 28	ENSP00000453317.1	Q92859-3

Frequencies

GnomAD3 genomes

AF:

0.00161

AC:

230

AN:

143302

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00548

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000695

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000259

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000984

GnomAD2 exomes

AF:

0.000190

AC:

AN:

26310

AF XY:

0.000124

show subpopulations

Gnomad AFR exome

AF:

0.0105

Gnomad AMR exome

AF:

0.000258

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000122

AC:

125

AN:

1020636

Hom.:

Cov.:

AF XY:

0.000113

AC XY:

AN XY:

496114

show subpopulations

African (AFR)

AF:

0.00558

AC:

109

AN:

19540

American (AMR)

AF:

0.000435

AC:

AN:

9196

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12190

East Asian (EAS)

AF:

0.00

AC:

AN:

17620

South Asian (SAS)

AF:

0.00

AC:

AN:

36526

European-Finnish (FIN)

AF:

0.00

AC:

AN:

15314

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2516

European-Non Finnish (NFE)

AF:

0.00000345

AC:

AN:

870156

Other (OTH)

AF:

0.000240

AC:

AN:

37578

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.00160

AC:

230

AN:

143454

Hom.:

Cov.:

AF XY:

0.00151

AC XY:

106

AN XY:

69974

show subpopulations

African (AFR)

AF:

0.00546

AC:

217

AN:

39734

American (AMR)

AF:

0.000693

AC:

AN:

14420

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3408

East Asian (EAS)

AF:

0.00

AC:

AN:

4024

South Asian (SAS)

AF:

0.000258

AC:

AN:

3878

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8962

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65800

Other (OTH)

AF:

0.000974

AC:

AN:

2054

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00107

Hom.:

Bravo

AF:

0.00175

ExAC

AF:

0.000187

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.43

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.35

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.052

LIST_S2

Uncertain

0.89

M_CAP

Pathogenic

0.80

MetaRNN

Benign

0.0090

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

0.0080

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-0.30

REVEL

Benign

0.056

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0090

Polyphen

0.23

Vest4

0.26

MutPred

0.50

Loss of disorder (P = 0.0165)

MVP

0.28

MPC

0.30

ClinPred

0.047

GERP RS

-0.014

PromoterAI

-0.0044

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.11

gMVP

0.45

Mutation Taster

=95/5

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over