rs16865416

Positions:

• chr1-201585195-G-A
• chr1-201585195-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001389617.1(NAV1):​c.-143-3344G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0484 in 152,244 control chromosomes in the GnomAD database, including 205 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 0.048 (205 hom., cov: 32)
• Consequence: NAV1 NM_001389617.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.365

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=-0.87).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0484 (7366/152244) while in subpopulation NFE AF= 0.0512 (3482/68004). AF 95% confidence interval is 0.0498. There are 205 homozygotes in gnomad4. There are 3528 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 7366 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAV1	NM_001389617.1	c.-143-3344G>A		intron_variant		ENST00000685211.1
NAV1	NM_001389615.1	c.-143-3344G>A		intron_variant
NAV1	NM_001389616.1	c.-32-37658G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAV1	ENST00000685211.1	c.-143-3344G>A		intron_variant			NM_001389617.1	P2

Frequencies

GnomAD3 genomes AF: 0.0484 AC: 7365 AN: 152126 Hom.: 204 Cov.: 32

Gnomad AFR AF: 0.0472

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.0465

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0244

Gnomad FIN AF: 0.0508

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0512

Gnomad OTH AF: 0.0602

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

GnomAD4 genome AF: 0.0484 AC: 7366 AN: 152244 Hom.: 205 Cov.: 32 AF XY: 0.0474 AC XY: 3528 AN XY: 74438

Gnomad4 AFR AF: 0.0471

Gnomad4 AMR AF: 0.0465

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0245

Gnomad4 FIN AF: 0.0508

Gnomad4 NFE AF: 0.0512

Gnomad4 OTH AF: 0.0600

Alfa AF: 0.0492 Hom.: 216

Bravo AF: 0.0483

Asia WGS AF: 0.0120 AC: 42 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.89
DANN	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16865416; hg19: chr1-201554323;