18-72850984-T-C

Position:

• chr18-72850984-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138966.5(NETO1):​c.469+7842A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 152,042 control chromosomes in the GnomAD database, including 29,114 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 0.61 (29114 hom., cov: 32)
• Consequence: NETO1 NM_138966.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.82

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]

NETO1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NETO1	NM_138966.5	c.469+7842A>G		intron_variant		ENST00000327305.11	NP_620416.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NETO1	ENST00000327305.11	c.469+7842A>G		intron_variant		1	NM_138966.5	ENSP00000313088.6
NETO1	ENST00000583169.5	c.469+7842A>G		intron_variant		1		ENSP00000464312.1
NETO1	ENST00000397929.5	c.466+7842A>G		intron_variant		1		ENSP00000381024.1
NETO1	ENST00000579730.2	n.302+13824A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91950 AN: 151924 Hom.: 29107 Cov.: 32

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.604

Gnomad EAS AF: 0.711

Gnomad SAS AF: 0.740

Gnomad FIN AF: 0.758

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.670

Gnomad OTH AF: 0.600

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

GnomAD4 genome AF: 0.605 AC: 91988 AN: 152042 Hom.: 29114 Cov.: 32 AF XY: 0.612 AC XY: 45494 AN XY: 74344

Gnomad4 AFR AF: 0.415

Gnomad4 AMR AF: 0.644

Gnomad4 ASJ AF: 0.604

Gnomad4 EAS AF: 0.711

Gnomad4 SAS AF: 0.741

Gnomad4 FIN AF: 0.758

Gnomad4 NFE AF: 0.670

Gnomad4 OTH AF: 0.602

Alfa AF: 0.653 Hom.: 66189

Bravo AF: 0.587

Asia WGS AF: 0.701 AC: 2439 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.059
DANN	Benign	0.35

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

LitVar

Other links and lift over

dbSNP: rs8098624; hg19: chr18-70518219;