15-73052780-G-A

Variant names:

• chr15-73052780-G-A
• NM_002499.4:c.105G>A
• NEO1 p.Arg35Arg

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_002499.4(NEO1):​c.105G>A​(p.Arg35Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NEO1 NM_002499.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.391
• 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP7: Synonymous conserved (PhyloP=0.391 with no splicing effect.

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.105G>A	p.Arg35Arg	synonymous	Exon 1 of 29	NP_002490.2	Q92859-1
	NEO1	NM_001419531.1		c.105G>A	p.Arg35Arg	synonymous	Exon 2 of 30	NP_001406460.1
	NEO1	NM_001172624.2		c.105G>A	p.Arg35Arg	synonymous	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.105G>A	p.Arg35Arg	synonymous	Exon 1 of 29	ENSP00000261908.6	Q92859-1
	NEO1	ENST00000558964.5	TSL:1	c.105G>A	p.Arg35Arg	synonymous	Exon 1 of 28	ENSP00000453200.1	Q92859-4
	NEO1	ENST00000560262.5	TSL:1	c.105G>A	p.Arg35Arg	synonymous	Exon 1 of 28	ENSP00000453317.1	Q92859-3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1034568 Hom.: 0 Cov.: 18 AF XY: 0.00 AC XY: 0 AN XY: 502844

African (AFR) AF: 0.00 AC: 0 AN: 19816

American (AMR) AF: 0.00 AC: 0 AN: 8122

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11736

East Asian (EAS) AF: 0.00 AC: 0 AN: 18158

South Asian (SAS) AF: 0.00 AC: 0 AN: 34138

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 17708

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2562

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 883808

Other (OTH) AF: 0.00 AC: 0 AN: 38520

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.3
DANN	Benign	0.96
PhyloP100		0.39
PromoterAI		0.017	Neutral

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr15-73345121;