rs586688

chr1-201661827-G-Achr1-201661827-G-T

Variant summary

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

The NM_001389617.1(NAV1):c.1618+12402G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,132 control chromosomes in the GnomAD database, including 5,084 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 0.22 (5084 hom., cov: 32)
• Consequence: NAV1 NM_001389617.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0130

Genes affected

NAV1 (HGNC:15989): (neuron navigator 1) This gene belongs to the neuron navigator family and is expressed predominantly in the nervous system. The encoded protein contains coiled-coil domains and a conserved AAA domain characteristic for ATPases associated with a variety of cellular activities. This gene is similar to unc-53, a Caenorhabditis elegans gene involved in axon guidance. The exact function of this gene is not known, but it is thought to play a role in in neuronal development and regeneration. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAV1	NM_001389617.1	c.1618+12402G>A		intron_variant		ENST00000685211.1
NAV1	NM_001389615.1	c.1618+12402G>A		intron_variant
NAV1	NM_001389616.1	c.1618+12402G>A		intron_variant
NAV1	NM_020443.5	c.757+12402G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAV1	ENST00000685211.1	c.1618+12402G>A		intron_variant			NM_001389617.1	P2
NAV1	ENST00000367296.8	c.757+12402G>A		intron_variant		5		A2
NAV1	ENST00000367302.5	c.796+12402G>A		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33125 AN: 152014 Hom.: 5049 Cov.: 32

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.0324

Gnomad SAS AF: 0.0896

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.218 AC: 33221 AN: 152132 Hom.: 5084 Cov.: 32 AF XY: 0.214 AC XY: 15919 AN XY: 74370

Gnomad4 AFR AF: 0.436

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.0326

Gnomad4 SAS AF: 0.0901

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.192

Alfa AF: 0.143 Hom.: 2265

Bravo AF: 0.224

Asia WGS AF: 0.109 AC: 379 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.1
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: rs586688; hg19: chr1-201630955;