chr15-73052719-C-A

Variant names:

• chr15-73052719-C-A
• rs748943546
• NM_002499.4:c.44C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002499.4(NEO1):​c.44C>A​(p.Ser15Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000141 in 1,358,392 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000073 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: NEO1 NM_002499.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.11
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05181977).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEO1	NM_002499.4	MANE Select	c.44C>A	p.Ser15Tyr	missense	Exon 1 of 29	NP_002490.2	Q92859-1
	NEO1	NM_001419531.1		c.44C>A	p.Ser15Tyr	missense	Exon 2 of 30	NP_001406460.1
	NEO1	NM_001172624.2		c.44C>A	p.Ser15Tyr	missense	Exon 2 of 29	NP_001166095.1	Q92859-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEO1	ENST00000261908.11	TSL:1 MANE Select	c.44C>A	p.Ser15Tyr	missense	Exon 1 of 29	ENSP00000261908.6	Q92859-1
	NEO1	ENST00000558964.5	TSL:1	c.44C>A	p.Ser15Tyr	missense	Exon 1 of 28	ENSP00000453200.1	Q92859-4
	NEO1	ENST00000560262.5	TSL:1	c.44C>A	p.Ser15Tyr	missense	Exon 1 of 28	ENSP00000453317.1	Q92859-3

Frequencies

GnomAD3 genomes AF: 0.0000731 AC: 11 AN: 150452 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000661

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: 0.000133

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000113 AC: 9 AN: 79972 AF XY: 0.000170

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000276

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000149 AC: 180 AN: 1207832 Hom.: 0 Cov.: 30 AF XY: 0.000173 AC XY: 103 AN XY: 595256

African (AFR) AF: 0.0000406 AC: 1 AN: 24658

American (AMR) AF: 0.0000455 AC: 1 AN: 21990

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19324

East Asian (EAS) AF: 0.00 AC: 0 AN: 24746

South Asian (SAS) AF: 0.00 AC: 0 AN: 57348

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28904

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3298

European-Non Finnish (NFE) AF: 0.000176 AC: 173 AN: 980346

Other (OTH) AF: 0.000106 AC: 5 AN: 47218

GnomAD4 genome AF: 0.0000731 AC: 11 AN: 150560 Hom.: 0 Cov.: 30 AF XY: 0.0000544 AC XY: 4 AN XY: 73522

African (AFR) AF: 0.0000242 AC: 1 AN: 41372

American (AMR) AF: 0.0000660 AC: 1 AN: 15154

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5000

South Asian (SAS) AF: 0.00 AC: 0 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10010

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000133 AC: 9 AN: 67462

Other (OTH) AF: 0.00 AC: 0 AN: 2100

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000102

ExAC AF: 0.000167 AC: 17

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.78	T
M_CAP	Pathogenic	0.63	D
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.1
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	0.040	N
REVEL	Benign	0.088
Sift	Benign	0.070	T
Sift4G	Uncertain	0.032	D
Polyphen		0.88	P
Vest4		0.29
MutPred		0.47		Loss of sheet (P = 3e-04)
MVP		0.60
MPC		0.26
ClinPred		0.054	T
GERP RS		0.013
PromoterAI		-0.045	Neutral
Varity_R		0.066
gMVP		0.43
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs748943546; hg19: chr15-73345060;