1-201777111-G-T

Variant names:

• chr1-201777111-G-T
• rs523218
• NM_001389617.1:c.2088-3310G>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.2088-3310G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0715 in 152,292 control chromosomes in the GnomAD database, including 789 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 0.072 (789 hom., cov: 32)
• Consequence: NAV1 NM_001389617.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.131
• Publications: 3 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]

LOC124904483 (HGNC:):

IPO9-AS1 (HGNC:40892): (IPO9 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.23 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAV1	NM_001389617.1	MANE Select	c.2088-3310G>T		intron	N/A	NP_001376546.1	A0A8I5KSE4
	NAV1	NM_001389616.1		c.2088-3310G>T		intron	N/A	NP_001376545.1
	NAV1	NM_001389615.1		c.2088-3310G>T		intron	N/A	NP_001376544.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAV1	ENST00000685211.1	MANE Select	c.2088-3310G>T		intron	N/A	ENSP00000510803.1	A0A8I5KSE4
	NAV1	ENST00000367295.5	TSL:1	c.54-3310G>T		intron	N/A	ENSP00000356264.1	Q8NEY1-5
	NAV1	ENST00000855601.1		c.1296-3310G>T		intron	N/A	ENSP00000525660.1

Frequencies

GnomAD3 genomes AF: 0.0715 AC: 10878 AN: 152174 Hom.: 784 Cov.: 32

Gnomad AFR AF: 0.0153

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.0425

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0605

Gnomad OTH AF: 0.0707

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

GnomAD4 genome AF: 0.0715 AC: 10890 AN: 152292 Hom.: 789 Cov.: 32 AF XY: 0.0775 AC XY: 5772 AN XY: 74464

African (AFR) AF: 0.0153 AC: 634 AN: 41558

American (AMR) AF: 0.199 AC: 3038 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 369 AN: 3472

East Asian (EAS) AF: 0.241 AC: 1246 AN: 5176

South Asian (SAS) AF: 0.162 AC: 783 AN: 4822

European-Finnish (FIN) AF: 0.0425 AC: 451 AN: 10620

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0605 AC: 4115 AN: 68028

Other (OTH) AF: 0.0709 AC: 150 AN: 2116

Alfa AF: 0.0715 Hom.: 1273

Bravo AF: 0.0812

Asia WGS AF: 0.197 AC: 682 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.75
DANN	Benign	0.64
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs523218; hg19: chr1-201746239;