Variant 1-201780563-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001389617.1(NAV1):c.2226+4C>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00568 in 1,614,134 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0038 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0059 ( 24 hom. )

Consequence

NAV1
NM_001389617.1 splice_donor_region, intron

Scores

Splicing: ADA: 0.0001371

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.06

Variant links:

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]

NAV1 links:

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

IPO9-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 1-201780563-C-T is Benign according to our data. Variant chr1-201780563-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2639784.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 573 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAV1	NM_001389617.1 linkuse as main transcript	c.2226+4C>T		splice_donor_region_variant, intron_variant		ENST00000685211.1	NP_001376546.1
IPO9-AS1	NR_046696.1 linkuse as main transcript	n.684+36664G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAV1	ENST00000685211.1 linkuse as main transcript	c.2226+4C>T		splice_donor_region_variant, intron_variant			NM_001389617.1	ENSP00000510803	P2
IPO9-AS1	ENST00000413035.5 linkuse as main transcript	n.684+36664G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00376

AC:

572

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.0141

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00614

Gnomad OTH

AF:

0.00480

GnomAD3 exomes

AF:

0.00376

AC:

946

AN:

251358

Hom.:

AF XY:

0.00393

AC XY:

534

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.00135

Gnomad AMR exome

AF:

0.00136

Gnomad ASJ exome

AF:

0.0119

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00120

Gnomad NFE exome

AF:

0.00618

Gnomad OTH exome

AF:

0.00440

GnomAD4 exome

AF:

0.00588

AC:

8602

AN:

1461844

Hom.:

Cov.:

AF XY:

0.00577

AC XY:

4194

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.000866

Gnomad4 AMR exome

AF:

0.00154

Gnomad4 ASJ exome

AF:

0.0108

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00159

Gnomad4 NFE exome

AF:

0.00698

Gnomad4 OTH exome

AF:

0.00599

GnomAD4 genome

AF:

0.00376

AC:

573

AN:

152290

Hom.:

Cov.:

AF XY:

0.00312

AC XY:

232

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00118

Gnomad4 AMR

AF:

0.00261

Gnomad4 ASJ

AF:

0.0141

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.00614

Gnomad4 OTH

AF:

0.00475

Alfa

AF:

0.00579

Hom.:

Bravo

AF:

0.00408

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00578

EpiControl

AF:

0.00593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2023

NAV1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00014

dbscSNV1_RF

Benign

0.040

SpliceAI score (max)

0.11

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over