15-73126400-ATTT-ATT

Variant names:

• chr15-73126400-AT-A
• rs747845315
• NM_002499.4:c.725-3delT

Variant summary

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

The NM_002499.4(NEO1):​c.725-3delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00287 in 143,870 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0029 (0 hom., cov: 32)
  • Exomes 𝑓: 0.33 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NEO1 NM_002499.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.242

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEO1	NM_002499.4	c.725-3delT		splice_region_variant, intron_variant	Intron 3 of 28	ENST00000261908.11	NP_002490.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEO1	ENST00000261908.11	c.725-16delT		intron_variant	Intron 3 of 28	1	NM_002499.4	ENSP00000261908.6

Frequencies

GnomAD3 genomes AF: 0.00280 AC: 403 AN: 143844 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00237

Gnomad ASJ AF: 0.00149

Gnomad EAS AF: 0.00120

Gnomad SAS AF: 0.000883

Gnomad FIN AF: 0.0147

Gnomad MID AF: 0.00336

Gnomad NFE AF: 0.00264

Gnomad OTH AF: 0.00360

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.328 AC: 290776 AN: 885556 Hom.: 0 Cov.: 0 AF XY: 0.331 AC XY: 146053 AN XY: 441658

Gnomad4 AFR exome AF: 0.331

Gnomad4 AMR exome AF: 0.329

Gnomad4 ASJ exome AF: 0.352

Gnomad4 EAS exome AF: 0.368

Gnomad4 SAS exome AF: 0.329

Gnomad4 FIN exome AF: 0.321

Gnomad4 NFE exome AF: 0.327

Gnomad4 OTH exome AF: 0.336

GnomAD4 genome AF: 0.00287 AC: 413 AN: 143870 Hom.: 0 Cov.: 32 AF XY: 0.00342 AC XY: 239 AN XY: 69890

Gnomad4 AFR AF: 0.00122

Gnomad4 AMR AF: 0.00244

Gnomad4 ASJ AF: 0.00149

Gnomad4 EAS AF: 0.00141

Gnomad4 SAS AF: 0.00155

Gnomad4 FIN AF: 0.0147

Gnomad4 NFE AF: 0.00264

Gnomad4 OTH AF: 0.00358

ClinVar

Not reported in ClinVar

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;