rs4777585

Positions:

• chr15-73083506-A-G
• chr15-73083506-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002499.4(NEO1):​c.130+30701A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 151,936 control chromosomes in the GnomAD database, including 39,193 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 0.71 (39193 hom., cov: 30)
• Consequence: NEO1 NM_002499.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.466

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEO1	NM_002499.4	c.130+30701A>G		intron_variant		ENST00000261908.11	NP_002490.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEO1	ENST00000261908.11	c.130+30701A>G		intron_variant		1	NM_002499.4	ENSP00000261908	A2
NEO1	ENST00000558964.5	c.130+30701A>G		intron_variant		1		ENSP00000453200	P4
NEO1	ENST00000560262.5	c.130+30701A>G		intron_variant		1		ENSP00000453317
NEO1	ENST00000339362.9	c.130+30701A>G		intron_variant		5		ENSP00000341198	A2

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107630 AN: 151820 Hom.: 39144 Cov.: 30

Gnomad AFR AF: 0.877

Gnomad AMI AF: 0.594

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.653

Gnomad OTH AF: 0.693

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

GnomAD4 genome AF: 0.709 AC: 107738 AN: 151936 Hom.: 39193 Cov.: 30 AF XY: 0.707 AC XY: 52495 AN XY: 74250

Gnomad4 AFR AF: 0.877

Gnomad4 AMR AF: 0.672

Gnomad4 ASJ AF: 0.579

Gnomad4 EAS AF: 0.433

Gnomad4 SAS AF: 0.626

Gnomad4 FIN AF: 0.692

Gnomad4 NFE AF: 0.653

Gnomad4 OTH AF: 0.695

Alfa AF: 0.651 Hom.: 12841

Bravo AF: 0.713

Asia WGS AF: 0.590 AC: 2054 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.6
DANN	Benign	0.14

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: rs4777585; hg19: chr15-73375847;