rs1854077

Variant names:

• chr1-201583710-A-G
• rs1854077
• NM_001389617.1:c.-143-4829A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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]

CSRP1-AS1 (HGNC:55856): (CSRP1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 7060 AD gene.

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.-143-4829A>G		intron	N/A	NP_001376546.1
	NAV1	NM_001389616.1		c.-32-39143A>G		intron	N/A	NP_001376545.1
	NAV1	NM_001389615.1		c.-143-4829A>G		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.-143-4829A>G		intron	N/A	ENSP00000510803.1
	CSRP1-AS1	ENST00000648727.1		n.713A>G		non_coding_transcript_exon	Exon 2 of 2
	CSRP1-AS1	ENST00000846697.1		n.175A>G		non_coding_transcript_exon	Exon 2 of 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

African (AFR) AF: 0.0409 AC: 1698 AN: 41542

American (AMR) AF: 0.0449 AC: 688 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 360 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.0244 AC: 118 AN: 4828

European-Finnish (FIN) AF: 0.0509 AC: 540 AN: 10602

Middle Eastern (MID) AF: 0.0685 AC: 20 AN: 292

European-Non Finnish (NFE) AF: 0.0510 AC: 3468 AN: 68030

Other (OTH) AF: 0.0563 AC: 119 AN: 2114

Alfa AF: 0.0498 Hom.: 102

Bravo AF: 0.0462

Asia WGS AF: 0.0120 AC: 42 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.67
PhyloP100		0.17

Splicing

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

Other links and lift over

dbSNP: rs1854077; hg19: chr1-201552838;