rs77078389

chr16-81351535-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_022041.4(GAN):c.168-48C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00853 in 802,626 control chromosomes in the GnomAD database, including 175 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0060 (24 hom., cov: 32)
  • Exomes 𝑓: 0.0091 (151 hom.)
• Consequence: GAN NM_022041.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.02

Genes affected

GAN (HGNC:4137): (gigaxonin) This gene encodes a member of the cytoskeletal BTB/kelch (Broad-Complex, Tramtrack and Bric a brac) repeat family. The encoded protein plays a role in neurofilament architecture and is involved in mediating the ubiquitination and degradation of some proteins. Defects in this gene are a cause of giant axonal neuropathy (GAN). [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 16-81351535-C-G is Benign according to our data. Variant chr16-81351535-C-G is described in ClinVar as [Benign]. Clinvar id is 261483.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAN	NM_022041.4	c.168-48C>G		intron_variant		ENST00000648994.2
GAN	NM_001377486.1	c.-357-2870C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAN	ENST00000648994.2	c.168-48C>G		intron_variant			NM_022041.4	P1
GAN	ENST00000648349.2	c.168-2870C>G		intron_variant, NMD_transcript_variant
GAN	ENST00000650388.1	c.168-5250C>G		intron_variant, NMD_transcript_variant
GAN	ENST00000674788.1	n.293-48C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00601 AC: 914 AN: 152108 Hom.: 24 Cov.: 32

Gnomad AFR AF: 0.00140

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0189

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0758

Gnomad SAS AF: 0.0193

Gnomad FIN AF: 0.00274

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000573

Gnomad OTH AF: 0.00574

GnomAD3 exomes AF: 0.0126 AC: 3033 AN: 240694 Hom.: 72 AF XY: 0.0114 AC XY: 1488 AN XY: 130722

Gnomad AFR exome AF: 0.00101

Gnomad AMR exome AF: 0.0314

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0730

Gnomad SAS exome AF: 0.0154

Gnomad FIN exome AF: 0.00299

Gnomad NFE exome AF: 0.000825

Gnomad OTH exome AF: 0.00844

GnomAD4 exome AF: 0.00912 AC: 5933 AN: 650400 Hom.: 151 Cov.: 8 AF XY: 0.00872 AC XY: 3080 AN XY: 353228

Gnomad4 AFR exome AF: 0.000677

Gnomad4 AMR exome AF: 0.0299

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0775

Gnomad4 SAS exome AF: 0.0157

Gnomad4 FIN exome AF: 0.00355

Gnomad4 NFE exome AF: 0.000783

Gnomad4 OTH exome AF: 0.00816

GnomAD4 genome AF: 0.00602 AC: 917 AN: 152226 Hom.: 24 Cov.: 32 AF XY: 0.00714 AC XY: 531 AN XY: 74416

Gnomad4 AFR AF: 0.00140

Gnomad4 AMR AF: 0.0191

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0756

Gnomad4 SAS AF: 0.0189

Gnomad4 FIN AF: 0.00274

Gnomad4 NFE AF: 0.000573

Gnomad4 OTH AF: 0.00757

Alfa AF: 0.00255 Hom.: 1

Bravo AF: 0.00710

Asia WGS AF: 0.0570 AC: 200 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	16
Dann	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs77078389; hg19: chr16-81385140;