15-73126400-ATT-A

Position:

• chr15-73126400-ATT-A

Variant summary

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

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 (no stars). There are indicators that this mutation may affect the branch point..

• 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 no assertion criteria provided 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 1 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 no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEO1	NM_002499.4	c.725-4_725-3del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000261908.11	NP_002490.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEO1	ENST00000261908.11	c.725-4_725-3del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_002499.4	ENSP00000261908	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: no assertion criteria provided

Submissions by phenotype

NEO1-related disorder Benign:1

Benign, no assertion criteria provided

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

Name	Calibrated prediction	Score	Prediction
BranchPoint Hunter		5.0

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;