chr18-72835818-A-G

Variant names:

• chr18-72835818-A-G
• rs17795324
• NM_138966.5:c.469+23008T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000327305.11(NETO1):​c.469+23008T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,206 control chromosomes in the GnomAD database, including 3,683 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 0.21 (3683 hom., cov: 32)
• Consequence: NETO1 ENST00000327305.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.474
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000327305.11. 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+23008T>C		intron	N/A	NP_620416.2
	NETO1	NM_001201465.3		c.469+23008T>C		intron	N/A	NP_001188394.2
	NETO1	NM_001354017.2		c.469+23008T>C		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+23008T>C		intron	N/A	ENSP00000313088.6
	NETO1	ENST00000583169.5	TSL:1	c.469+23008T>C		intron	N/A	ENSP00000464312.1
	NETO1	ENST00000397929.5	TSL:1	c.467-499T>C		intron	N/A	ENSP00000381024.1

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31890 AN: 152088 Hom.: 3684 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.210 AC: 31899 AN: 152206 Hom.: 3683 Cov.: 32 AF XY: 0.209 AC XY: 15524 AN XY: 74394

African (AFR) AF: 0.125 AC: 5209 AN: 41546

American (AMR) AF: 0.195 AC: 2987 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1111 AN: 3466

East Asian (EAS) AF: 0.250 AC: 1292 AN: 5170

South Asian (SAS) AF: 0.110 AC: 533 AN: 4828

European-Finnish (FIN) AF: 0.279 AC: 2948 AN: 10584

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.250 AC: 17003 AN: 68006

Other (OTH) AF: 0.237 AC: 500 AN: 2112

Alfa AF: 0.242 Hom.: 15853

Bravo AF: 0.203

Asia WGS AF: 0.178 AC: 619 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.14
DANN	Benign	0.22
PhyloP100		-0.47
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: rs17795324; hg19: chr18-70503053;