dbSNP rs747845315: NEO1:c.725-6_725-3delTTTT (chr15-73126400-ATTTT-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002499.4(NEO1):c.725-6_725-3delTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,167,904 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: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

NEO1
NM_002499.4 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.02

Publications

0 publications found

Variant links:

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]

NEO1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NEO1	NM_002499.4	MANE Select	c.725-6_725-3delTTTT	splice_region intron	N/A	NP_002490.2	Q92859-1
NEO1	NM_001419531.1		c.725-6_725-3delTTTT	splice_region intron	N/A	NP_001406460.1
NEO1	NM_001172624.2		c.725-6_725-3delTTTT	splice_region intron	N/A	NP_001166095.1	Q92859-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NEO1	ENST00000261908.11	TSL:1 MANE Select	c.725-16_725-13delTTTT	intron	N/A	ENSP00000261908.6	Q92859-1
NEO1	ENST00000558964.5	TSL:1	c.725-16_725-13delTTTT	intron	N/A	ENSP00000453200.1	Q92859-4
NEO1	ENST00000560262.5	TSL:1	c.725-16_725-13delTTTT	intron	N/A	ENSP00000453317.1	Q92859-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1167904

Hom.:

AF XY:

0.00000172

AC XY:

AN XY:

582492

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

25780

American (AMR)

AF:

0.0000322

AC:

AN:

31012

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21270

East Asian (EAS)

AF:

0.00

AC:

AN:

34446

South Asian (SAS)

AF:

0.0000151

AC:

AN:

66392

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40234

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4732

European-Non Finnish (NFE)

AF:

0.00000223

AC:

AN:

894988

Other (OTH)

AF:

0.00

AC:

AN:

49050

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over