rs614452

Variant names:

• chr1-201584435-T-G
• rs614452
• NM_001389617.1:c.-143-4104T>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.-143-4104T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.099 in 152,252 control chromosomes in the GnomAD database, including 1,004 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 0.099 (1004 hom., cov: 33)
• Consequence: NAV1 NM_001389617.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0180
• 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]

CSRP1-AS1 (HGNC:55856): (CSRP1 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAV1	NM_001389617.1	c.-143-4104T>G		intron_variant	Intron 1 of 33	ENST00000685211.1	NP_001376546.1
NAV1	NM_001389616.1	c.-32-38418T>G		intron_variant	Intron 1 of 31		NP_001376545.1
NAV1	NM_001389615.1	c.-143-4104T>G		intron_variant	Intron 1 of 30		NP_001376544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAV1	ENST00000685211.1	c.-143-4104T>G		intron_variant	Intron 1 of 33		NM_001389617.1	ENSP00000510803.1

Frequencies

GnomAD3 genomes AF: 0.0989 AC: 15053 AN: 152134 Hom.: 1004 Cov.: 33

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.0687

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0548

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0553

Gnomad OTH AF: 0.0937

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

GnomAD4 genome AF: 0.0990 AC: 15073 AN: 152252 Hom.: 1004 Cov.: 33 AF XY: 0.0992 AC XY: 7386 AN XY: 74436

African (AFR) AF: 0.178 AC: 7402 AN: 41530

American (AMR) AF: 0.0685 AC: 1048 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 599 AN: 3468

East Asian (EAS) AF: 0.160 AC: 828 AN: 5180

South Asian (SAS) AF: 0.116 AC: 561 AN: 4830

European-Finnish (FIN) AF: 0.0548 AC: 582 AN: 10612

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

European-Non Finnish (NFE) AF: 0.0553 AC: 3763 AN: 68016

Other (OTH) AF: 0.0941 AC: 199 AN: 2114

Alfa AF: 0.0694 Hom.: 687

Bravo AF: 0.104

Asia WGS AF: 0.121 AC: 418 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.2
DANN	Benign	0.51
PhyloP100		0.018

Splicing

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

Other links and lift over

dbSNP: rs614452; hg19: chr1-201553563;