NM_001389617.1:c.2088-29G>C

Variant names:

• chr1-201780392-G-C
• rs529581
• NM_001389617.1:c.2088-29G>C

Variant summary

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

The NM_001389617.1(NAV1):​c.2088-29G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 1,611,378 control chromosomes in the GnomAD database, including 118,814 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 0.33 (9217 hom., cov: 32)
  • Exomes 𝑓: 0.38 (109597 hom.)
• Consequence: NAV1 NM_001389617.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62
• Publications: 10 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]

IPO9-AS1 (HGNC:40892): (IPO9 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001389617.1. 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
	NAV1	NM_001389617.1	MANE Select	c.2088-29G>C		intron	N/A	NP_001376546.1
	NAV1	NM_001389616.1		c.2088-29G>C		intron	N/A	NP_001376545.1
	NAV1	NM_001389615.1		c.2088-29G>C		intron	N/A	NP_001376544.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAV1	ENST00000685211.1	MANE Select	c.2088-29G>C		intron	N/A	ENSP00000510803.1
	NAV1	ENST00000367295.5	TSL:1	c.54-29G>C		intron	N/A	ENSP00000356264.1
	NAV1	ENST00000367296.8	TSL:5	c.1227-29G>C		intron	N/A	ENSP00000356265.4

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50221 AN: 151956 Hom.: 9211 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.360

GnomAD2 exomes AF: 0.370 AC: 92736 AN: 250738 AF XY: 0.366

Gnomad AFR exome AF: 0.162

Gnomad AMR exome AF: 0.485

Gnomad ASJ exome AF: 0.447

Gnomad EAS exome AF: 0.317

Gnomad FIN exome AF: 0.385

Gnomad NFE exome AF: 0.396

Gnomad OTH exome AF: 0.392

GnomAD4 exome AF: 0.383 AC: 558357 AN: 1459304 Hom.: 109597 Cov.: 34 AF XY: 0.379 AC XY: 275312 AN XY: 725818

African (AFR) AF: 0.157 AC: 5233 AN: 33422

American (AMR) AF: 0.478 AC: 21348 AN: 44638

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 11741 AN: 26108

East Asian (EAS) AF: 0.325 AC: 12905 AN: 39662

South Asian (SAS) AF: 0.249 AC: 21480 AN: 86156

European-Finnish (FIN) AF: 0.393 AC: 20981 AN: 53396

Middle Eastern (MID) AF: 0.263 AC: 1515 AN: 5756

European-Non Finnish (NFE) AF: 0.397 AC: 440607 AN: 1109862

Other (OTH) AF: 0.374 AC: 22547 AN: 60304

GnomAD4 genome AF: 0.330 AC: 50249 AN: 152074 Hom.: 9217 Cov.: 32 AF XY: 0.331 AC XY: 24630 AN XY: 74320

African (AFR) AF: 0.167 AC: 6934 AN: 41486

American (AMR) AF: 0.432 AC: 6599 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 1570 AN: 3472

East Asian (EAS) AF: 0.315 AC: 1630 AN: 5168

South Asian (SAS) AF: 0.253 AC: 1219 AN: 4818

European-Finnish (FIN) AF: 0.387 AC: 4087 AN: 10554

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.399 AC: 27090 AN: 67974

Other (OTH) AF: 0.358 AC: 755 AN: 2108

Alfa AF: 0.295 Hom.: 1246

Bravo AF: 0.328

Asia WGS AF: 0.301 AC: 1046 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.022
DANN	Benign	0.56
PhyloP100		-1.6
PromoterAI		0.0094	Neutral
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: rs529581; hg19: chr1-201749520; COSMIC: COSV55213889; COSMIC: COSV55213889;