rs8035499

Variant names:

• chr15-73135883-T-A
• rs8035499
• NM_002499.4:c.879-8T>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002499.4(NEO1):​c.879-8T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0815 in 1,426,022 control chromosomes in the GnomAD database, including 5,421 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1935 hom., cov: 29)
  • Exomes 𝑓: 0.076 (3486 hom.)
• Consequence: NEO1 NM_002499.4 splice_region, intron
• Scores: Splicing: ADA: 0.01718
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.88
• Publications: 4 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 15-73135883-T-A is Benign according to our data. Variant chr15-73135883-T-A is described in ClinVar as Benign. ClinVar VariationId is 771006.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

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.879-8T>A		splice_region intron	N/A	NP_002490.2	Q92859-1
	NEO1	NM_001419531.1		c.879-8T>A		splice_region intron	N/A	NP_001406460.1
	NEO1	NM_001172624.2		c.879-8T>A		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.879-8T>A		splice_region intron	N/A	ENSP00000261908.6	Q92859-1
	NEO1	ENST00000558964.5	TSL:1	c.879-8T>A		splice_region intron	N/A	ENSP00000453200.1	Q92859-4
	NEO1	ENST00000560262.5	TSL:1	c.879-8T>A		splice_region intron	N/A	ENSP00000453317.1	Q92859-3

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19246 AN: 148854 Hom.: 1936 Cov.: 29

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.0656

Gnomad AMR AF: 0.0698

Gnomad ASJ AF: 0.0591

Gnomad EAS AF: 0.000972

Gnomad SAS AF: 0.0136

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.0833

Gnomad NFE AF: 0.0772

Gnomad OTH AF: 0.0960

GnomAD2 exomes AF: 0.0935 AC: 8688 AN: 92886 AF XY: 0.0863

Gnomad AFR exome AF: 0.299

Gnomad AMR exome AF: 0.0487

Gnomad ASJ exome AF: 0.0732

Gnomad EAS exome AF: 0.000268

Gnomad FIN exome AF: 0.183

Gnomad NFE exome AF: 0.0937

Gnomad OTH exome AF: 0.0778

GnomAD4 exome AF: 0.0760 AC: 97030 AN: 1277070 Hom.: 3486 Cov.: 32 AF XY: 0.0742 AC XY: 46665 AN XY: 628914

African (AFR) AF: 0.273 AC: 7333 AN: 26890

American (AMR) AF: 0.0488 AC: 1088 AN: 22286

Ashkenazi Jewish (ASJ) AF: 0.0587 AC: 1236 AN: 21072

East Asian (EAS) AF: 0.000262 AC: 9 AN: 34408

South Asian (SAS) AF: 0.0143 AC: 900 AN: 63076

European-Finnish (FIN) AF: 0.136 AC: 4986 AN: 36632

Middle Eastern (MID) AF: 0.0532 AC: 222 AN: 4174

European-Non Finnish (NFE) AF: 0.0761 AC: 77280 AN: 1015834

Other (OTH) AF: 0.0754 AC: 3976 AN: 52698

GnomAD4 genome AF: 0.129 AC: 19251 AN: 148952 Hom.: 1935 Cov.: 29 AF XY: 0.128 AC XY: 9269 AN XY: 72612

African (AFR) AF: 0.278 AC: 11195 AN: 40302

American (AMR) AF: 0.0696 AC: 1046 AN: 15020

Ashkenazi Jewish (ASJ) AF: 0.0591 AC: 204 AN: 3452

East Asian (EAS) AF: 0.000974 AC: 5 AN: 5134

South Asian (SAS) AF: 0.0136 AC: 64 AN: 4718

European-Finnish (FIN) AF: 0.129 AC: 1258 AN: 9726

Middle Eastern (MID) AF: 0.0862 AC: 25 AN: 290

European-Non Finnish (NFE) AF: 0.0772 AC: 5200 AN: 67348

Other (OTH) AF: 0.0946 AC: 195 AN: 2062

Alfa AF: 0.0935 Hom.: 175

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	NEO1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.8
DANN	Benign	0.50
PhyloP100		2.9
PromoterAI		0.012	Neutral
Mutation Taster		=53/47	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.017
dbscSNV1_RF	Benign	0.12
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: rs8035499; hg19: chr15-73428224;