1-201661827-G-A

Variant names:

• chr1-201661827-G-A
• rs586688
• NM_001389617.1:c.1618+12402G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NAV1	NM_001389617.1	c.1618+12402G>A		intron_variant	Intron 5 of 33	ENST00000685211.1	NP_001376546.1
NAV1	NM_001389616.1	c.1618+12402G>A		intron_variant	Intron 4 of 31		NP_001376545.1
NAV1	NM_001389615.1	c.1618+12402G>A		intron_variant	Intron 5 of 30		NP_001376544.1
NAV1	NM_020443.5	c.757+12402G>A		intron_variant	Intron 1 of 29		NP_065176.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAV1	ENST00000685211.1	c.1618+12402G>A		intron_variant	Intron 5 of 33		NM_001389617.1	ENSP00000510803.1
NAV1	ENST00000367296.8	c.757+12402G>A		intron_variant	Intron 1 of 29	5		ENSP00000356265.4
NAV1	ENST00000367302.5	c.796+12402G>A		intron_variant	Intron 3 of 29	5		ENSP00000356271.1
NAV1	ENST00000850636.1	c.826+32320G>A		intron_variant	Intron 4 of 6			ENSP00000520915.1

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

African (AFR) AF: 0.436 AC: 18086 AN: 41460

American (AMR) AF: 0.122 AC: 1861 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 527 AN: 3470

East Asian (EAS) AF: 0.0326 AC: 169 AN: 5180

South Asian (SAS) AF: 0.0901 AC: 434 AN: 4818

European-Finnish (FIN) AF: 0.155 AC: 1641 AN: 10590

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 9990 AN: 68004

Other (OTH) AF: 0.192 AC: 406 AN: 2114

Alfa AF: 0.169 Hom.: 5829

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
PhyloP100		-0.013
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: rs586688; hg19: chr1-201630955;