15-73135863-CTTTT-C

Position:

• chr15-73135863-CTTTT-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP6

The NM_002499.4(NEO1):​c.879-11_879-8del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00423 in 1,276,814 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0046 (0 hom.)
• Consequence: NEO1 NM_002499.4 intron
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.206

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 15-73135863-CTTTT-C is Benign according to our data. Variant chr15-73135863-CTTTT-C is described in ClinVar as [Benign]. Clinvar id is 3038312.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEO1	NM_002499.4	c.879-11_879-8del		intron_variant		ENST00000261908.11	NP_002490.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEO1	ENST00000261908.11	c.879-11_879-8del		intron_variant		1	NM_002499.4	ENSP00000261908	A2
NEO1	ENST00000558964.5	c.879-11_879-8del		intron_variant		1		ENSP00000453200	P4
NEO1	ENST00000560262.5	c.879-11_879-8del		intron_variant		1		ENSP00000453317
NEO1	ENST00000339362.9	c.879-11_879-8del		intron_variant		5		ENSP00000341198	A2

Frequencies

GnomAD3 genomes AF: 0.00000888 AC: 1 AN: 112674 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000904

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: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0138 AC: 427 AN: 30970 Hom.: 0 AF XY: 0.0154 AC XY: 242 AN XY: 15732

Gnomad AFR exome AF: 0.00840

Gnomad AMR exome AF: 0.0211

Gnomad ASJ exome AF: 0.0208

Gnomad EAS exome AF: 0.0149

Gnomad SAS exome AF: 0.0222

Gnomad FIN exome AF: 0.00780

Gnomad NFE exome AF: 0.0110

Gnomad OTH exome AF: 0.0124

GnomAD4 exome AF: 0.00464 AC: 5400 AN: 1164164 Hom.: 0 AF XY: 0.00495 AC XY: 2808 AN XY: 567766

Gnomad4 AFR exome AF: 0.00361

Gnomad4 AMR exome AF: 0.0143

Gnomad4 ASJ exome AF: 0.00781

Gnomad4 EAS exome AF: 0.00814

Gnomad4 SAS exome AF: 0.0104

Gnomad4 FIN exome AF: 0.00747

Gnomad4 NFE exome AF: 0.00393

Gnomad4 OTH exome AF: 0.00513

GnomAD4 genome AF: 0.00000888 AC: 1 AN: 112650 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 53726

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000904

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

NEO1-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 25, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

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: rs376822156; hg19: chr15-73428204;