1-201585195-G-A

Variant names:

• chr1-201585195-G-A
• rs16865416
• NM_001389617.1:c.-143-3344G>A

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.-143-3344G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0484 in 152,244 control chromosomes in the GnomAD database, including 205 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 0.048 (205 hom., cov: 32)
• Consequence: NAV1 NM_001389617.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.365
• 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=-0.87).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0484 (7366/152244) while in subpopulation NFE AF = 0.0512 (3482/68004). AF 95% confidence interval is 0.0498. There are 205 homozygotes in GnomAd4. There are 3528 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 7366 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAV1	NM_001389617.1	MANE Select	c.-143-3344G>A		intron	N/A	NP_001376546.1	A0A8I5KSE4
	NAV1	NM_001389616.1		c.-32-37658G>A		intron	N/A	NP_001376545.1
	NAV1	NM_001389615.1		c.-143-3344G>A		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.-143-3344G>A		intron	N/A	ENSP00000510803.1	A0A8I5KSE4
	NAV1	ENST00000855601.1		c.-143-3344G>A		intron	N/A	ENSP00000525660.1
	NAV1	ENST00000935746.1		c.-32-37658G>A		intron	N/A	ENSP00000605805.1

Frequencies

GnomAD3 genomes AF: 0.0484 AC: 7365 AN: 152126 Hom.: 204 Cov.: 32

Gnomad AFR AF: 0.0472

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.0465

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0244

Gnomad FIN AF: 0.0508

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0512

Gnomad OTH AF: 0.0602

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

GnomAD4 genome AF: 0.0484 AC: 7366 AN: 152244 Hom.: 205 Cov.: 32 AF XY: 0.0474 AC XY: 3528 AN XY: 74438

African (AFR) AF: 0.0471 AC: 1956 AN: 41528

American (AMR) AF: 0.0465 AC: 711 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 363 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.0245 AC: 118 AN: 4824

European-Finnish (FIN) AF: 0.0508 AC: 539 AN: 10608

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0512 AC: 3482 AN: 68004

Other (OTH) AF: 0.0600 AC: 127 AN: 2116

Alfa AF: 0.0498 Hom.: 276

Bravo AF: 0.0483

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	-0.87
CADD	Benign	0.89
DANN	Benign	0.59
PhyloP100		-0.36

Splicing

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

Other links and lift over

dbSNP: rs16865416; hg19: chr1-201554323;