rs1527047

Positions:

• chr12-77379769-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XR_007063383.1(LOC124902972):​n.1516A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 151,934 control chromosomes in the GnomAD database, including 24,927 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 0.57 (24927 hom., cov: 31)
  • Exomes 𝑓: 0.43 (0 hom.)
• Consequence: LOC124902972 XR_007063383.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.678

Genes affected

LOC124902972 (HGNC:):

NAV3 (HGNC:15998): (neuron navigator 3) 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. Multiple alternatively spliced transcript variants for this gene have been described but only one has had its full-length nature determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124902972	XR_007063383.1	n.1516A>G		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAV3	ENST00000550042.2	c.-337+54555A>G		intron_variant		5
	ENST00000552736.2			upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86337 AN: 151802 Hom.: 24931 Cov.: 31

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.590

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.621

Gnomad OTH AF: 0.589

GnomAD4 exome AF: 0.429 AC: 6 AN: 14 Hom.: 0 AF XY: 0.500 AC XY: 3 AN XY: 6

Gnomad4 AFR exome AF: 0.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.568 AC: 86354 AN: 151920 Hom.: 24927 Cov.: 31 AF XY: 0.561 AC XY: 41679 AN XY: 74244

Gnomad4 AFR AF: 0.527

Gnomad4 AMR AF: 0.546

Gnomad4 ASJ AF: 0.549

Gnomad4 EAS AF: 0.462

Gnomad4 SAS AF: 0.395

Gnomad4 FIN AF: 0.556

Gnomad4 NFE AF: 0.621

Gnomad4 OTH AF: 0.584

Alfa AF: 0.600 Hom.: 12650

Bravo AF: 0.570

Asia WGS AF: 0.456 AC: 1587 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.42
DANN	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1527047; hg19: chr12-77773549;