rs1854077

Positions:

• chr1-201583710-A-G

Variant summary

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

The NM_001389617.1(NAV1):​c.-143-4829A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0464 in 152,282 control chromosomes in the GnomAD database, including 186 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 0.046 (186 hom., cov: 33)
• Consequence: NAV1 NM_001389617.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.173

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0464 (7060/152282) while in subpopulation NFE AF= 0.051 (3468/68030). AF 95% confidence interval is 0.0496. There are 186 homozygotes in gnomad4. There are 3399 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 7060 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAV1	NM_001389617.1	c.-143-4829A>G		intron_variant		ENST00000685211.1	NP_001376546.1
NAV1	NM_001389615.1	c.-143-4829A>G		intron_variant			NP_001376544.1
NAV1	NM_001389616.1	c.-32-39143A>G		intron_variant			NP_001376545.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAV1	ENST00000685211.1	c.-143-4829A>G		intron_variant			NM_001389617.1	ENSP00000510803	P2
	ENST00000648727.1	n.713A>G		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes AF: 0.0464 AC: 7059 AN: 152164 Hom.: 185 Cov.: 33

Gnomad AFR AF: 0.0409

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.0450

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0244

Gnomad FIN AF: 0.0509

Gnomad MID AF: 0.0669

Gnomad NFE AF: 0.0510

Gnomad OTH AF: 0.0564

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

GnomAD4 genome AF: 0.0464 AC: 7060 AN: 152282 Hom.: 186 Cov.: 33 AF XY: 0.0456 AC XY: 3399 AN XY: 74458

Gnomad4 AFR AF: 0.0409

Gnomad4 AMR AF: 0.0449

Gnomad4 ASJ AF: 0.104

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0244

Gnomad4 FIN AF: 0.0509

Gnomad4 NFE AF: 0.0510

Gnomad4 OTH AF: 0.0563

Alfa AF: 0.0496 Hom.: 95

Bravo AF: 0.0462

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	-0.89
CADD	Benign	1.4
DANN	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1854077; hg19: chr1-201552838;