chr1-201592492-C-T

Variant names:

• chr1-201592492-C-T
• rs545372
• NM_001389617.1:c.-33+3843C>T

Variant summary

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

The NM_001389617.1(NAV1):​c.-33+3843C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0973 in 152,154 control chromosomes in the GnomAD database, including 960 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 0.097 (960 hom., cov: 32)
• Consequence: NAV1 NM_001389617.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.63
• Publications: 1 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.17 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.-33+3843C>T		intron	N/A	NP_001376546.1
	NAV1	NM_001389616.1		c.-32-30361C>T		intron	N/A	NP_001376545.1
	NAV1	NM_001389615.1		c.-33+3843C>T		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.-33+3843C>T		intron	N/A	ENSP00000510803.1
	NAV1	ENST00000850636.1		c.-33+3843C>T		intron	N/A	ENSP00000520915.1

Frequencies

GnomAD3 genomes AF: 0.0973 AC: 14789 AN: 152034 Hom.: 960 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.0678

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.0550

Gnomad MID AF: 0.0892

Gnomad NFE AF: 0.0552

Gnomad OTH AF: 0.0936

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

GnomAD4 genome AF: 0.0973 AC: 14805 AN: 152154 Hom.: 960 Cov.: 32 AF XY: 0.0978 AC XY: 7274 AN XY: 74382

African (AFR) AF: 0.173 AC: 7178 AN: 41508

American (AMR) AF: 0.0676 AC: 1033 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 601 AN: 3470

East Asian (EAS) AF: 0.159 AC: 819 AN: 5160

South Asian (SAS) AF: 0.115 AC: 553 AN: 4818

European-Finnish (FIN) AF: 0.0550 AC: 582 AN: 10590

Middle Eastern (MID) AF: 0.0925 AC: 27 AN: 292

European-Non Finnish (NFE) AF: 0.0552 AC: 3753 AN: 68006

Other (OTH) AF: 0.0926 AC: 196 AN: 2116

Alfa AF: 0.0714 Hom.: 2203

Bravo AF: 0.102

Asia WGS AF: 0.116 AC: 402 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.30
DANN	Benign	0.41
PhyloP100		-2.6

Splicing

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

Other links and lift over

dbSNP: rs545372; hg19: chr1-201561620;