15-73122739-C-T

Variant names:

• chr15-73122739-C-T
• rs148761830
• NM_002499.4:c.663C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_002499.4(NEO1):​c.663C>T​(p.Cys221Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0016 in 1,614,086 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0016 (17 hom.)
• Consequence: NEO1 NM_002499.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.229
• Publications: 1 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 15-73122739-C-T is Benign according to our data. Variant chr15-73122739-C-T is described in ClinVar as Benign. ClinVar VariationId is 777250.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.229 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 17 gene

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.663C>T	p.Cys221Cys	synonymous	Exon 3 of 29	NP_002490.2	Q92859-1
	NEO1	NM_001419531.1		c.663C>T	p.Cys221Cys	synonymous	Exon 4 of 30	NP_001406460.1
	NEO1	NM_001172624.2		c.663C>T	p.Cys221Cys	synonymous	Exon 4 of 29	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.663C>T	p.Cys221Cys	synonymous	Exon 3 of 29	ENSP00000261908.6	Q92859-1
	NEO1	ENST00000558964.5	TSL:1	c.663C>T	p.Cys221Cys	synonymous	Exon 3 of 28	ENSP00000453200.1	Q92859-4
	NEO1	ENST00000560262.5	TSL:1	c.663C>T	p.Cys221Cys	synonymous	Exon 3 of 28	ENSP00000453317.1	Q92859-3

Frequencies

GnomAD3 genomes AF: 0.00140 AC: 213 AN: 152100 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00367

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00436

Gnomad FIN AF: 0.000473

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00160

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00170 AC: 428 AN: 251254 AF XY: 0.00204

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.000896

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.00153

Gnomad OTH exome AF: 0.00294

GnomAD4 exome AF: 0.00162 AC: 2375 AN: 1461868 Hom.: 17 Cov.: 31 AF XY: 0.00174 AC XY: 1263 AN XY: 727238

African (AFR) AF: 0.000179 AC: 6 AN: 33480

American (AMR) AF: 0.00136 AC: 61 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00570 AC: 492 AN: 86258

European-Finnish (FIN) AF: 0.000337 AC: 18 AN: 53420

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.00155 AC: 1728 AN: 1111992

Other (OTH) AF: 0.00109 AC: 66 AN: 60396

GnomAD4 genome AF: 0.00139 AC: 212 AN: 152218 Hom.: 1 Cov.: 31 AF XY: 0.00120 AC XY: 89 AN XY: 74408

African (AFR) AF: 0.000385 AC: 16 AN: 41520

American (AMR) AF: 0.00360 AC: 55 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00436 AC: 21 AN: 4816

European-Finnish (FIN) AF: 0.000473 AC: 5 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00160 AC: 109 AN: 68032

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00107 Hom.: 0

Bravo AF: 0.00174

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00207

EpiControl AF: 0.00255

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	6.7
DANN	Benign	0.45
PhyloP100		0.23
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs148761830; hg19: chr15-73415080; COSMIC: COSV56076979;