15-73122547-A-G

Variant names:

• chr15-73122547-A-G
• rs144328581
• NM_002499.4:c.471A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BS1 BS2

The NM_002499.4(NEO1):​c.471A>G​(p.Gln157Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000687 in 1,614,068 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00091 (3 hom., cov: 31)
  • Exomes 𝑓: 0.00066 (7 hom.)
• Consequence: NEO1 NM_002499.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.676

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP6: Variant 15-73122547-A-G is Benign according to our data. Variant chr15-73122547-A-G is described in ClinVar as [Benign]. Clinvar id is 3042512.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.676 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000913 (139/152288) while in subpopulation EAS AF= 0.0216 (112/5190). AF 95% confidence interval is 0.0183. There are 3 homozygotes in gnomad4. There are 71 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEO1	NM_002499.4	c.471A>G	p.Gln157Gln	synonymous_variant	Exon 3 of 29	ENST00000261908.11	NP_002490.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEO1	ENST00000261908.11	c.471A>G	p.Gln157Gln	synonymous_variant	Exon 3 of 29	1	NM_002499.4	ENSP00000261908.6
NEO1	ENST00000558964.5	c.471A>G	p.Gln157Gln	synonymous_variant	Exon 3 of 28	1		ENSP00000453200.1
NEO1	ENST00000560262.5	c.471A>G	p.Gln157Gln	synonymous_variant	Exon 3 of 28	1		ENSP00000453317.1
NEO1	ENST00000339362.9	c.471A>G	p.Gln157Gln	synonymous_variant	Exon 4 of 30	5		ENSP00000341198.5

Frequencies

GnomAD3 genomes AF: 0.000920 AC: 140 AN: 152170 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0217

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00179 AC: 449 AN: 251202 Hom.: 5 AF XY: 0.00169 AC XY: 230 AN XY: 135766

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0235

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.000664 AC: 970 AN: 1461780 Hom.: 7 Cov.: 31 AF XY: 0.000677 AC XY: 492 AN XY: 727176

Gnomad4 AFR exome AF: 0.000119

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0209

Gnomad4 SAS exome AF: 0.000128

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000989

Gnomad4 OTH exome AF: 0.00185

GnomAD4 genome AF: 0.000913 AC: 139 AN: 152288 Hom.: 3 Cov.: 31 AF XY: 0.000953 AC XY: 71 AN XY: 74468

Gnomad4 AFR AF: 0.000361

Gnomad4 AMR AF: 0.000392

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0216

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.000246 Hom.: 0

Bravo AF: 0.000880

Asia WGS AF: 0.00924 AC: 32 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

NEO1-related disorder Benign:1

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as 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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	3.4
DANN	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs144328581; hg19: chr15-73414888;