1-201778996-G-A

Position:

• chr1-201778996-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001389617.1(NAV1):​c.2088-1425G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 152,076 control chromosomes in the GnomAD database, including 9,154 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 0.33 (9154 hom., cov: 32)
• Consequence: NAV1 NM_001389617.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.407

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]

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAV1	NM_001389617.1	c.2088-1425G>A		intron_variant		ENST00000685211.1
IPO9-AS1	NR_046696.1	n.684+38231C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAV1	ENST00000685211.1	c.2088-1425G>A		intron_variant			NM_001389617.1	P2
IPO9-AS1	ENST00000413035.5	n.684+38231C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49971 AN: 151958 Hom.: 9149 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.335

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.356

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

GnomAD4 genome AF: 0.329 AC: 49993 AN: 152076 Hom.: 9154 Cov.: 32 AF XY: 0.330 AC XY: 24516 AN XY: 74346

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.432

Gnomad4 ASJ AF: 0.452

Gnomad4 EAS AF: 0.315

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.386

Gnomad4 NFE AF: 0.398

Gnomad4 OTH AF: 0.355

Alfa AF: 0.356 Hom.: 1275

Bravo AF: 0.327

Asia WGS AF: 0.296 AC: 1028 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.1
DANN	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs665770; hg19: chr1-201748124;