15-73126400-ATT-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_002499.4(NEO1):c.725-4_725-3del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00294 in 1,277,346 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000021 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0033 (0 hom.)
• Consequence: NEO1 NM_002499.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.346

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 15-73126400-ATT-A is Benign according to our data. Variant chr15-73126400-ATT-A is described in ClinVar as [Benign]. Clinvar id is 3044362.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEO1	NM_002499.4	c.725-4_725-3del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000261908.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEO1	ENST00000261908.11	c.725-4_725-3del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_002499.4	A2

Frequencies

GnomAD3 genomes AF: 0.0000208 AC: 3 AN: 144366 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000110

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000306

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00331 AC: 3754 AN: 1132980 Hom.: 0 AF XY: 0.00346 AC XY: 1958 AN XY: 565124

Gnomad4 AFR exome AF: 0.00312

Gnomad4 AMR exome AF: 0.00675

Gnomad4 ASJ exome AF: 0.00445

Gnomad4 EAS exome AF: 0.00331

Gnomad4 SAS exome AF: 0.00651

Gnomad4 FIN exome AF: 0.00295

Gnomad4 NFE exome AF: 0.00293

Gnomad4 OTH exome AF: 0.00382

GnomAD4 genome AF: 0.0000208 AC: 3 AN: 144366 Hom.: 0 Cov.: 32 AF XY: 0.0000428 AC XY: 3 AN XY: 70116

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000110

Gnomad4 NFE AF: 0.0000306

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00657 Hom.: 8

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

NEO1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 06, 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: rs747845315; hg19: chr15-73418741;