rs17086492

Variant names:

• chr18-72855835-T-C
• rs17086492
• NM_138966.5:c.469+2991A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138966.5(NETO1):​c.469+2991A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.025 in 152,286 control chromosomes in the GnomAD database, including 129 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.025 (129 hom., cov: 32)
• Consequence: NETO1 NM_138966.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.556
• Publications: 1 publications found

Genes affected

NETO1 (HGNC:13823): (neuropilin and tolloid like 1) This gene encodes a transmembrane protein containing two extracellular CUB domains followed by a low-density lipoprotein class A (LDLa) domain. This protein is thought to play a critical role in spatial learning and memory by regulating the function of synaptic N-methyl-D-aspartic acid receptor complexes in the hippocampus. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2017]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138966.5. 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
	NETO1	NM_138966.5	MANE Select	c.469+2991A>G		intron	N/A	NP_620416.2
	NETO1	NM_001201465.3		c.469+2991A>G		intron	N/A	NP_001188394.2
	NETO1	NM_001354017.2		c.469+2991A>G		intron	N/A	NP_001340946.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NETO1	ENST00000327305.11	TSL:1 MANE Select	c.469+2991A>G		intron	N/A	ENSP00000313088.6
	NETO1	ENST00000583169.5	TSL:1	c.469+2991A>G		intron	N/A	ENSP00000464312.1
	NETO1	ENST00000397929.5	TSL:1	c.466+2991A>G		intron	N/A	ENSP00000381024.1

Frequencies

GnomAD3 genomes AF: 0.0250 AC: 3808 AN: 152168 Hom.: 127 Cov.: 32

Gnomad AFR AF: 0.0527

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0453

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.0454

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000691

Gnomad OTH AF: 0.0229

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0250 AC: 3811 AN: 152286 Hom.: 129 Cov.: 32 AF XY: 0.0264 AC XY: 1965 AN XY: 74446

African (AFR) AF: 0.0527 AC: 2190 AN: 41548

American (AMR) AF: 0.0453 AC: 693 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.118 AC: 613 AN: 5176

South Asian (SAS) AF: 0.0446 AC: 215 AN: 4822

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10620

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000691 AC: 47 AN: 68042

Other (OTH) AF: 0.0227 AC: 48 AN: 2114

Alfa AF: 0.0137 Hom.: 23

Bravo AF: 0.0305

Asia WGS AF: 0.0830 AC: 290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.85
DANN	Benign	0.73
PhyloP100		-0.56
Mutation Taster		=100/0	polymorphism (auto)

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: rs17086492; hg19: chr18-70523070;