rs41418949

Positions:

• chr18-72774833-C-T

Variant summary

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

The NM_138966.5(NETO1):​c.868+8845G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0472 in 152,164 control chromosomes in the GnomAD database, including 264 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 0.047 (264 hom., cov: 33)
• Consequence: NETO1 NM_138966.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0987 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NETO1	NM_138966.5	c.868+8845G>A		intron_variant		ENST00000327305.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NETO1	ENST00000327305.11	c.868+8845G>A		intron_variant		1	NM_138966.5	P1
NETO1	ENST00000583169.5	c.868+8845G>A		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.0472 AC: 7172 AN: 152046 Hom.: 261 Cov.: 33

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.0282

Gnomad ASJ AF: 0.0237

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0184

Gnomad FIN AF: 0.0145

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0307

Gnomad OTH AF: 0.0372

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

GnomAD4 genome AF: 0.0472 AC: 7183 AN: 152164 Hom.: 264 Cov.: 33 AF XY: 0.0454 AC XY: 3377 AN XY: 74370

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.0281

Gnomad4 ASJ AF: 0.0237

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0180

Gnomad4 FIN AF: 0.0145

Gnomad4 NFE AF: 0.0307

Gnomad4 OTH AF: 0.0369

Alfa AF: 0.0320 Hom.: 155

Bravo AF: 0.0504

Asia WGS AF: 0.0150 AC: 52 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.21
DANN	Benign	0.42

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: rs41418949; hg19: chr18-70442068;