15-73135863-CTTTTT-C

Position:

• chr15-73135863-CTTTTT-C

Variant summary

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

The NM_002499.4(NEO1):​c.879-12_879-8del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000768 in 1,289,884 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00084 (0 hom.)
• Consequence: NEO1 NM_002499.4 intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.206

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 15-73135863-CTTTTT-C is Benign according to our data. Variant chr15-73135863-CTTTTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 3048145.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.879-12_879-8del		intron_variant		ENST00000261908.11	NP_002490.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEO1	ENST00000261908.11	c.879-12_879-8del		intron_variant		1	NM_002499.4	ENSP00000261908	A2
NEO1	ENST00000558964.5	c.879-12_879-8del		intron_variant		1		ENSP00000453200	P4
NEO1	ENST00000560262.5	c.879-12_879-8del		intron_variant		1		ENSP00000453317
NEO1	ENST00000339362.9	c.879-12_879-8del		intron_variant		5		ENSP00000341198	A2

Frequencies

GnomAD3 genomes AF: 0.00000888 AC: 1 AN: 112676 Hom.: 0 Cov.: 30

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: 0.000172

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00391 AC: 121 AN: 30970 Hom.: 0 AF XY: 0.00426 AC XY: 67 AN XY: 15732

Gnomad AFR exome AF: 0.00315

Gnomad AMR exome AF: 0.00549

Gnomad ASJ exome AF: 0.00486

Gnomad EAS exome AF: 0.00569

Gnomad SAS exome AF: 0.00511

Gnomad FIN exome AF: 0.00111

Gnomad NFE exome AF: 0.00313

Gnomad OTH exome AF: 0.00564

GnomAD4 exome AF: 0.000840 AC: 989 AN: 1177208 Hom.: 0 AF XY: 0.000918 AC XY: 527 AN XY: 573976

Gnomad4 AFR exome AF: 0.000617

Gnomad4 AMR exome AF: 0.00304

Gnomad4 ASJ exome AF: 0.00190

Gnomad4 EAS exome AF: 0.00172

Gnomad4 SAS exome AF: 0.00223

Gnomad4 FIN exome AF: 0.00149

Gnomad4 NFE exome AF: 0.000660

Gnomad4 OTH exome AF: 0.00112

GnomAD4 genome AF: 0.00000888 AC: 1 AN: 112676 Hom.: 0 Cov.: 30 AF XY: 0.0000186 AC XY: 1 AN XY: 53726

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: 0.000172

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000576 Hom.: 2

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

NEO1-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 06, 2020

This variant is classified as likely 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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs376822156; hg19: chr15-73428204;