chr1-201648725-C-A

Variant names:

• chr1-201648725-C-A
• rs571656889
• NM_001389617.1:c.918C>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001389617.1(NAV1):​c.918C>A​(p.Gly306Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00147 in 1,414,162 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0070 (16 hom., cov: 32)
  • Exomes 𝑓: 0.00080 (8 hom.)
• Consequence: NAV1 NM_001389617.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.839

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BP6: Variant 1-201648725-C-A is Benign according to our data. Variant chr1-201648725-C-A is described in ClinVar as [Benign]. Clinvar id is 767742.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.839 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00701 (1066/152122) while in subpopulation AFR AF = 0.0233 (968/41518). AF 95% confidence interval is 0.0221. There are 16 homozygotes in GnomAd4. There are 498 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.
• BS2: High AC in GnomAd4 at 1066 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAV1	NM_001389617.1	c.918C>A	p.Gly306Gly	synonymous_variant	Exon 5 of 34	ENST00000685211.1	NP_001376546.1
NAV1	NM_001389616.1	c.918C>A	p.Gly306Gly	synonymous_variant	Exon 4 of 32		NP_001376545.1
NAV1	NM_001389615.1	c.918C>A	p.Gly306Gly	synonymous_variant	Exon 5 of 31		NP_001376544.1
NAV1	NM_020443.5	c.57C>A	p.Gly19Gly	synonymous_variant	Exon 1 of 30		NP_065176.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAV1	ENST00000685211.1	c.918C>A	p.Gly306Gly	synonymous_variant	Exon 5 of 34		NM_001389617.1	ENSP00000510803.1
NAV1	ENST00000367296.8	c.57C>A	p.Gly19Gly	synonymous_variant	Exon 1 of 30	5		ENSP00000356265.4
NAV1	ENST00000367302.5	c.96C>A	p.Gly32Gly	synonymous_variant	Exon 3 of 30	5		ENSP00000356271.1

Frequencies

GnomAD3 genomes AF: 0.00693 AC: 1053 AN: 152014 Hom.: 16 Cov.: 32

Gnomad AFR AF: 0.0231

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00354

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00641

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.00861

GnomAD2 exomes AF: 0.000851 AC: 44 AN: 51688 AF XY: 0.000818

Gnomad AFR exome AF: 0.0273

Gnomad AMR exome AF: 0.00170

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000463

Gnomad OTH exome AF: 0.000697

GnomAD4 exome AF: 0.000797 AC: 1006 AN: 1262040 Hom.: 8 Cov.: 54 AF XY: 0.000758 AC XY: 469 AN XY: 619042

Gnomad4 AFR exome AF: 0.0225 AC: 576 AN: 25636

Gnomad4 AMR exome AF: 0.00241 AC: 46 AN: 19068

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 20956

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 27732

Gnomad4 SAS exome AF: 0.000118 AC: 7 AN: 59446

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 32600

Gnomad4 NFE exome AF: 0.000240 AC: 245 AN: 1020486

Gnomad4 Remaining exome AF: 0.00231 AC: 120 AN: 52010

GnomAD4 genome AF: 0.00701 AC: 1066 AN: 152122 Hom.: 16 Cov.: 32 AF XY: 0.00670 AC XY: 498 AN XY: 74358

Gnomad4 AFR AF: 0.0233 AC: 0.0233152 AN: 0.0233152

Gnomad4 AMR AF: 0.00353 AC: 0.00353311 AN: 0.00353311

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000207 AC: 0.000207469 AN: 0.000207469

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000338 AC: 0.000338395 AN: 0.000338395

Gnomad4 OTH AF: 0.00852 AC: 0.00852273 AN: 0.00852273

Alfa AF: 0.000280 Hom.: 0

Bravo AF: 0.00801

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 04, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	13
DANN	Benign	0.95
Mutation Taster		=100/0	polymorphism

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: rs571656889; hg19: chr1-201617853;