rs1109070

Variant names:

• chr18-72856344-T-C
• rs1109070
• NM_138966.5:c.469+2482A>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+2482A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 152,042 control chromosomes in the GnomAD database, including 6,476 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 0.29 (6476 hom., cov: 32)
• Consequence: NETO1 NM_138966.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.627
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NETO1	NM_138966.5	c.469+2482A>G		intron_variant	Intron 4 of 10	ENST00000327305.11	NP_620416.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NETO1	ENST00000327305.11	c.469+2482A>G		intron_variant	Intron 4 of 10	1	NM_138966.5	ENSP00000313088.6
NETO1	ENST00000583169.5	c.469+2482A>G		intron_variant	Intron 4 of 10	1		ENSP00000464312.1
NETO1	ENST00000397929.5	c.466+2482A>G		intron_variant	Intron 4 of 4	1		ENSP00000381024.1
NETO1	ENST00000579730.2	n.302+8464A>G		intron_variant	Intron 3 of 3	5

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43458 AN: 151922 Hom.: 6478 Cov.: 32

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.305

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

GnomAD4 genome AF: 0.286 AC: 43478 AN: 152042 Hom.: 6476 Cov.: 32 AF XY: 0.280 AC XY: 20838 AN XY: 74356

African (AFR) AF: 0.259 AC: 10754 AN: 41444

American (AMR) AF: 0.285 AC: 4353 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1277 AN: 3470

East Asian (EAS) AF: 0.183 AC: 945 AN: 5168

South Asian (SAS) AF: 0.177 AC: 857 AN: 4830

European-Finnish (FIN) AF: 0.234 AC: 2478 AN: 10574

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.320 AC: 21726 AN: 67982

Other (OTH) AF: 0.305 AC: 641 AN: 2104

Alfa AF: 0.302 Hom.: 1836

Bravo AF: 0.289

Asia WGS AF: 0.176 AC: 612 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.33
DANN	Benign	0.39
PhyloP100		-0.63
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: rs1109070; hg19: chr18-70523579;