18-72844576-T-A

Variant names:

• chr18-72844576-T-A
• rs6566674
• NM_138966.5:c.469+14250A>T

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+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
• Publications: 3 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 (NFE) allele frequency at 95% confidence interval = 0.9 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+14250A>T		intron	N/A	NP_620416.2
	NETO1	NM_001201465.3		c.469+14250A>T		intron	N/A	NP_001188394.2
	NETO1	NM_001354017.2		c.469+14250A>T		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+14250A>T		intron	N/A	ENSP00000313088.6
	NETO1	ENST00000583169.5	TSL:1	c.469+14250A>T		intron	N/A	ENSP00000464312.1
	NETO1	ENST00000397929.5	TSL:1	c.467-9257A>T		intron	N/A	ENSP00000381024.1

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

African (AFR) AF: 0.733 AC: 30422 AN: 41512

American (AMR) AF: 0.884 AC: 13520 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.897 AC: 3114 AN: 3472

East Asian (EAS) AF: 0.809 AC: 4193 AN: 5182

South Asian (SAS) AF: 0.870 AC: 4195 AN: 4824

European-Finnish (FIN) AF: 0.954 AC: 10128 AN: 10612

Middle Eastern (MID) AF: 0.795 AC: 232 AN: 292

European-Non Finnish (NFE) AF: 0.906 AC: 61652 AN: 68024

Other (OTH) AF: 0.869 AC: 1837 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.7
DANN	Benign	0.50
PhyloP100		0.39
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: rs6566674; hg19: chr18-70511811;