rs625436

Variant names:

• chr1-201592547-A-G
• rs625436
• NM_001389617.1:c.-33+3898A>G

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+3898A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0956 in 152,192 control chromosomes in the GnomAD database, including 919 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 0.096 (919 hom., cov: 32)
• Consequence: NAV1 NM_001389617.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75
• 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]

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 = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAV1	NM_001389617.1	c.-33+3898A>G		intron_variant	Intron 2 of 33	ENST00000685211.1	NP_001376546.1
NAV1	NM_001389616.1	c.-32-30306A>G		intron_variant	Intron 1 of 31		NP_001376545.1
NAV1	NM_001389615.1	c.-33+3898A>G		intron_variant	Intron 2 of 30		NP_001376544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAV1	ENST00000685211.1	c.-33+3898A>G		intron_variant	Intron 2 of 33		NM_001389617.1	ENSP00000510803.1
NAV1	ENST00000850636.1	c.-33+3898A>G		intron_variant	Intron 2 of 6			ENSP00000520915.1

Frequencies

GnomAD3 genomes AF: 0.0955 AC: 14530 AN: 152074 Hom.: 919 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.0677

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.0549

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0552

Gnomad OTH AF: 0.0918

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

GnomAD4 genome AF: 0.0956 AC: 14544 AN: 152192 Hom.: 919 Cov.: 32 AF XY: 0.0960 AC XY: 7140 AN XY: 74400

African (AFR) AF: 0.166 AC: 6904 AN: 41504

American (AMR) AF: 0.0675 AC: 1032 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 603 AN: 3472

East Asian (EAS) AF: 0.160 AC: 826 AN: 5170

South Asian (SAS) AF: 0.117 AC: 563 AN: 4820

European-Finnish (FIN) AF: 0.0549 AC: 582 AN: 10604

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0552 AC: 3751 AN: 68004

Other (OTH) AF: 0.0908 AC: 192 AN: 2114

Alfa AF: 0.0697 Hom.: 257

Bravo AF: 0.0997

Asia WGS AF: 0.115 AC: 400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.38
DANN	Benign	0.28
PhyloP100		-1.7

Splicing

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

Other links and lift over

dbSNP: rs625436; hg19: chr1-201561675;