rs1564345

Variant names:

• chr15-73205533-T-C
• rs1564345
• NM_002499.4:c.1291+27106T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002499.4(NEO1):​c.1291+27106T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 152,100 control chromosomes in the GnomAD database, including 10,622 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.36 (10622 hom., cov: 32)
• Consequence: NEO1 NM_002499.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.144
• Publications: 3 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEO1	NM_002499.4	c.1291+27106T>C		intron_variant	Intron 7 of 28	ENST00000261908.11	NP_002490.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEO1	ENST00000261908.11	c.1291+27106T>C		intron_variant	Intron 7 of 28	1	NM_002499.4	ENSP00000261908.6

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54578 AN: 151982 Hom.: 10605 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.394

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.359 AC: 54616 AN: 152100 Hom.: 10622 Cov.: 32 AF XY: 0.359 AC XY: 26666 AN XY: 74348

African (AFR) AF: 0.215 AC: 8929 AN: 41504

American (AMR) AF: 0.468 AC: 7151 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 1058 AN: 3470

East Asian (EAS) AF: 0.325 AC: 1669 AN: 5142

South Asian (SAS) AF: 0.355 AC: 1710 AN: 4820

European-Finnish (FIN) AF: 0.368 AC: 3887 AN: 10572

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.426 AC: 28958 AN: 67998

Other (OTH) AF: 0.393 AC: 831 AN: 2112

Alfa AF: 0.380 Hom.: 3006

Bravo AF: 0.360

Asia WGS AF: 0.369 AC: 1286 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.9
DANN	Benign	0.76
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

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: rs1564345; hg19: chr15-73497874;