15-73126400-ATTTT-AT

Variant names:

• chr15-73126400-ATTT-A
• rs747845315
• NM_002499.4:c.725-5_725-3delTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_002499.4(NEO1):​c.725-5_725-3delTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000702 in 1,310,514 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 0.000014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000077 (0 hom.)
• Consequence: NEO1 NM_002499.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02
• 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.725-5_725-3delTTT		splice_region intron	N/A	NP_002490.2	Q92859-1
	NEO1	NM_001419531.1		c.725-5_725-3delTTT		splice_region intron	N/A	NP_001406460.1
	NEO1	NM_001172624.2		c.725-5_725-3delTTT		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.725-16_725-14delTTT		intron	N/A	ENSP00000261908.6	Q92859-1
	NEO1	ENST00000558964.5	TSL:1	c.725-16_725-14delTTT		intron	N/A	ENSP00000453200.1	Q92859-4
	NEO1	ENST00000560262.5	TSL:1	c.725-16_725-14delTTT		intron	N/A	ENSP00000453317.1	Q92859-3

Frequencies

GnomAD3 genomes AF: 0.0000138 AC: 2 AN: 144422 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: 0.000220

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000325 AC: 35 AN: 107830 AF XY: 0.000437

Gnomad AFR exome AF: 0.000271

Gnomad AMR exome AF: 0.000882

Gnomad ASJ exome AF: 0.000215

Gnomad EAS exome AF: 0.000386

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000213

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000772 AC: 90 AN: 1166092 Hom.: 0 AF XY: 0.0000911 AC XY: 53 AN XY: 581586

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

African (AFR) AF: 0.0000388 AC: 1 AN: 25744

American (AMR) AF: 0.000291 AC: 9 AN: 30976

Ashkenazi Jewish (ASJ) AF: 0.0000941 AC: 2 AN: 21258

East Asian (EAS) AF: 0.000145 AC: 5 AN: 34404

South Asian (SAS) AF: 0.000241 AC: 16 AN: 66264

European-Finnish (FIN) AF: 0.000174 AC: 7 AN: 40186

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4724

European-Non Finnish (NFE) AF: 0.0000526 AC: 47 AN: 893548

Other (OTH) AF: 0.0000612 AC: 3 AN: 48988

⚠️ 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: 0.0000138 AC: 2 AN: 144422 Hom.: 0 Cov.: 32 AF XY: 0.0000143 AC XY: 1 AN XY: 70150

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

African (AFR) AF: 0.00 AC: 0 AN: 39422

American (AMR) AF: 0.00 AC: 0 AN: 14398

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3350

East Asian (EAS) AF: 0.00 AC: 0 AN: 4990

South Asian (SAS) AF: 0.00 AC: 0 AN: 4532

European-Finnish (FIN) AF: 0.000220 AC: 2 AN: 9110

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 300

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65478

Other (OTH) AF: 0.00 AC: 0 AN: 1948

⚠️ 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.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.0
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

Other links and lift over

dbSNP: rs747845315; hg19: chr15-73418741;