chr18-72808537-T-C

Variant names:

• chr18-72808537-T-C
• rs17086334
• NM_138966.5:c.470-14133A>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.470-14133A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00805 in 152,126 control chromosomes in the GnomAD database, including 25 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 0.0080 (25 hom., cov: 32)
• Consequence: NETO1 NM_138966.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.188
• 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 = 0.081 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NETO1	NM_138966.5	c.470-14133A>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.470-14133A>G		intron_variant	Intron 4 of 10	1	NM_138966.5	ENSP00000313088.6
NETO1	ENST00000583169.5	c.470-14133A>G		intron_variant	Intron 4 of 10	1		ENSP00000464312.1
NETO1	ENST00000579730.2	n.303-24631A>G		intron_variant	Intron 3 of 3	5

Frequencies

GnomAD3 genomes AF: 0.00805 AC: 1223 AN: 152008 Hom.: 25 Cov.: 32

Gnomad AFR AF: 0.00343

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0138

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0878

Gnomad SAS AF: 0.0543

Gnomad FIN AF: 0.00870

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000780

Gnomad OTH AF: 0.00431

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

GnomAD4 genome AF: 0.00805 AC: 1224 AN: 152126 Hom.: 25 Cov.: 32 AF XY: 0.00972 AC XY: 723 AN XY: 74360

African (AFR) AF: 0.00342 AC: 142 AN: 41528

American (AMR) AF: 0.0137 AC: 209 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.0876 AC: 453 AN: 5170

South Asian (SAS) AF: 0.0541 AC: 261 AN: 4820

European-Finnish (FIN) AF: 0.00870 AC: 92 AN: 10580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000780 AC: 53 AN: 67974

Other (OTH) AF: 0.00663 AC: 14 AN: 2112

Alfa AF: 0.00434 Hom.: 2

Bravo AF: 0.00693

Asia WGS AF: 0.0680 AC: 234 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	2.4
DANN	Benign	0.60
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism

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: rs17086334; hg19: chr18-70475772;