rs495198

Variant names:

• chr1-201636988-G-A
• rs495198
• NM_001389617.1:c.826+7481G>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.826+7481G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.809 in 152,212 control chromosomes in the GnomAD database, including 49,971 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 0.81 (49971 hom., cov: 32)
• Consequence: NAV1 NM_001389617.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91
• Publications: 6 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]

LOC124904482 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.853 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAV1	NM_001389617.1	c.826+7481G>A		intron_variant	Intron 4 of 33	ENST00000685211.1	NP_001376546.1
LOC124904482	XR_007066789.1	n.10997C>T		non_coding_transcript_exon_variant	Exon 1 of 2
NAV1	NM_001389616.1	c.826+7481G>A		intron_variant	Intron 3 of 31		NP_001376545.1
NAV1	NM_001389615.1	c.826+7481G>A		intron_variant	Intron 4 of 30		NP_001376544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAV1	ENST00000685211.1	c.826+7481G>A		intron_variant	Intron 4 of 33		NM_001389617.1	ENSP00000510803.1
NAV1	ENST00000367302.5	c.4+7481G>A		intron_variant	Intron 2 of 29	5		ENSP00000356271.1
NAV1	ENST00000850636.1	c.826+7481G>A		intron_variant	Intron 4 of 6			ENSP00000520915.1

Frequencies

GnomAD3 genomes AF: 0.809 AC: 122998 AN: 152094 Hom.: 49918 Cov.: 32

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.623

Gnomad AMR AF: 0.865

Gnomad ASJ AF: 0.790

Gnomad EAS AF: 0.682

Gnomad SAS AF: 0.652

Gnomad FIN AF: 0.794

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.819

Gnomad OTH AF: 0.804

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

GnomAD4 genome AF: 0.809 AC: 123106 AN: 152212 Hom.: 49971 Cov.: 32 AF XY: 0.803 AC XY: 59760 AN XY: 74420

African (AFR) AF: 0.815 AC: 33849 AN: 41510

American (AMR) AF: 0.866 AC: 13253 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.790 AC: 2742 AN: 3470

East Asian (EAS) AF: 0.683 AC: 3539 AN: 5182

South Asian (SAS) AF: 0.652 AC: 3141 AN: 4814

European-Finnish (FIN) AF: 0.794 AC: 8413 AN: 10592

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.819 AC: 55685 AN: 68012

Other (OTH) AF: 0.799 AC: 1690 AN: 2114

Alfa AF: 0.815 Hom.: 23864

Bravo AF: 0.818

Asia WGS AF: 0.704 AC: 2450 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.092
DANN	Benign	0.61
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs495198; hg19: chr1-201606116;