chr18-72844576-T-A

Position:

• chr18-72844576-T-A

Variant summary

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

The NM_138966.5(NETO1):​c.469+14250A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.855 in 152,244 control chromosomes in the GnomAD database, including 56,091 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 0.85 (56091 hom., cov: 33)
• Consequence: NETO1 NM_138966.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.391

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NETO1	NM_138966.5	c.469+14250A>T		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+14250A>T		intron_variant		1	NM_138966.5	ENSP00000313088.6
NETO1	ENST00000583169.5	c.469+14250A>T		intron_variant		1		ENSP00000464312.1
NETO1	ENST00000397929.5	c.467-9257A>T		intron_variant		1		ENSP00000381024.1
NETO1	ENST00000579730.2	n.302+20232A>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.855 AC: 130015 AN: 152126 Hom.: 56061 Cov.: 33

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.887

Gnomad AMR AF: 0.884

Gnomad ASJ AF: 0.897

Gnomad EAS AF: 0.809

Gnomad SAS AF: 0.870

Gnomad FIN AF: 0.954

Gnomad MID AF: 0.803

Gnomad NFE AF: 0.906

Gnomad OTH AF: 0.869

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

GnomAD4 genome AF: 0.855 AC: 130102 AN: 152244 Hom.: 56091 Cov.: 33 AF XY: 0.857 AC XY: 63783 AN XY: 74450

Gnomad4 AFR AF: 0.733

Gnomad4 AMR AF: 0.884

Gnomad4 ASJ AF: 0.897

Gnomad4 EAS AF: 0.809

Gnomad4 SAS AF: 0.870

Gnomad4 FIN AF: 0.954

Gnomad4 NFE AF: 0.906

Gnomad4 OTH AF: 0.869

Alfa AF: 0.882 Hom.: 7393

Bravo AF: 0.846

Asia WGS AF: 0.841 AC: 2925 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.7
DANN	Benign	0.50

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: rs6566674; hg19: chr18-70511811;