chr18-72851755-C-T

Variant names:

• chr18-72851755-C-T
• rs8098760
• NM_138966.5:c.469+7071G>A

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+7071G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0265 in 152,126 control chromosomes in the GnomAD database, including 133 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 0.026 (133 hom., cov: 33)
• Consequence: NETO1 NM_138966.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0893 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NETO1	NM_138966.5	MANE Select	c.469+7071G>A		intron	N/A	NP_620416.2
	NETO1	NM_001201465.3		c.469+7071G>A		intron	N/A	NP_001188394.2
	NETO1	NM_001354017.2		c.469+7071G>A		intron	N/A	NP_001340946.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NETO1	ENST00000327305.11	TSL:1 MANE Select	c.469+7071G>A		intron	N/A	ENSP00000313088.6
	NETO1	ENST00000583169.5	TSL:1	c.469+7071G>A		intron	N/A	ENSP00000464312.1
	NETO1	ENST00000397929.5	TSL:1	c.466+7071G>A		intron	N/A	ENSP00000381024.1

Frequencies

GnomAD3 genomes AF: 0.0264 AC: 4020 AN: 152008 Hom.: 130 Cov.: 33

Gnomad AFR AF: 0.0612

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0445

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0966

Gnomad SAS AF: 0.0456

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000618

Gnomad OTH AF: 0.0215

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

GnomAD4 genome AF: 0.0265 AC: 4025 AN: 152126 Hom.: 133 Cov.: 33 AF XY: 0.0277 AC XY: 2058 AN XY: 74394

African (AFR) AF: 0.0612 AC: 2540 AN: 41472

American (AMR) AF: 0.0446 AC: 682 AN: 15288

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

East Asian (EAS) AF: 0.0963 AC: 498 AN: 5174

South Asian (SAS) AF: 0.0450 AC: 217 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10576

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000618 AC: 42 AN: 68004

Other (OTH) AF: 0.0213 AC: 45 AN: 2114

Alfa AF: 0.0119 Hom.: 69

Bravo AF: 0.0323

Asia WGS AF: 0.0770 AC: 268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.16
DANN	Benign	0.82
PhyloP100		-1.0
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: rs8098760; hg19: chr18-70518990;