rs747845315

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr15-73126400-ATTT-A
• chr15-73126400-ATTT-AT
• chr15-73126400-ATTT-ATT
• chr15-73126400-ATTT-ATTTT
• chr15-73126400-ATTT-ATTTTT

Variant summary

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

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

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEO1	NM_002499.4	c.725-5_725-3delTTT		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.725-16_725-14delTTT		intron_variant	Intron 3 of 28	1	NM_002499.4	ENSP00000261908.6

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

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

Gnomad4 AFR exome AF: 0.0000388

Gnomad4 AMR exome AF: 0.000291

Gnomad4 ASJ exome AF: 0.0000941

Gnomad4 EAS exome AF: 0.000145

Gnomad4 SAS exome AF: 0.000241

Gnomad4 FIN exome AF: 0.000174

Gnomad4 NFE exome AF: 0.0000526

Gnomad4 OTH exome AF: 0.0000612

GnomAD4 genome AF: 0.0000138 AC: 2 AN: 144422 Hom.: 0 Cov.: 32 AF XY: 0.0000143 AC XY: 1 AN XY: 70150

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: 0.000220

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

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;