15-73126400-ATTTT-ATTT

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. Variant has been reported in ClinVar as (no stars).

• 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
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.725-3delT		splice_region intron	N/A	NP_002490.2	Q92859-1
	NEO1	NM_001419531.1		c.725-3delT		splice_region intron	N/A	NP_001406460.1
	NEO1	NM_001172624.2		c.725-3delT		splice_region intron	N/A	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.725-16delT		intron	N/A	ENSP00000261908.6	Q92859-1
	NEO1	ENST00000558964.5	TSL:1	c.725-16delT		intron	N/A	ENSP00000453200.1	Q92859-4
	NEO1	ENST00000560262.5	TSL:1	c.725-16delT		intron	N/A	ENSP00000453317.1	Q92859-3

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

GnomAD2 exomes AF: 0.403 AC: 43444 AN: 107830 AF XY: 0.409

Gnomad AFR exome AF: 0.389

Gnomad AMR exome AF: 0.416

Gnomad ASJ exome AF: 0.426

Gnomad EAS exome AF: 0.401

Gnomad FIN exome AF: 0.353

Gnomad NFE exome AF: 0.401

Gnomad OTH exome AF: 0.408

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.331 AC: 6417 AN: 19388

American (AMR) AF: 0.329 AC: 8437 AN: 25616

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 5824 AN: 16524

East Asian (EAS) AF: 0.368 AC: 8900 AN: 24194

South Asian (SAS) AF: 0.329 AC: 18292 AN: 55594

European-Finnish (FIN) AF: 0.321 AC: 9892 AN: 30852

Middle Eastern (MID) AF: 0.235 AC: 907 AN: 3852

European-Non Finnish (NFE) AF: 0.327 AC: 219629 AN: 672452

Other (OTH) AF: 0.336 AC: 12478 AN: 37084

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00122 AC: 48 AN: 39436

American (AMR) AF: 0.00244 AC: 35 AN: 14362

Ashkenazi Jewish (ASJ) AF: 0.00149 AC: 5 AN: 3348

East Asian (EAS) AF: 0.00141 AC: 7 AN: 4968

South Asian (SAS) AF: 0.00155 AC: 7 AN: 4514

European-Finnish (FIN) AF: 0.0147 AC: 131 AN: 8940

Middle Eastern (MID) AF: 0.00368 AC: 1 AN: 272

European-Non Finnish (NFE) AF: 0.00264 AC: 172 AN: 65182

Other (OTH) AF: 0.00358 AC: 7 AN: 1954

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0778 Hom.: 8

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.24
BranchPoint Hunter		5.0
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs747845315; hg19: chr15-73418741; COSMIC: COSV56069595;