Genetic Variant GAN:c.168-48C>G (chr16-81351535-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.02

Variant links:

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]

GAN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
GAN	NM_022041.4 link	c.168-48C>G		intron_variant	Intron 1 of 10	ENST00000648994.2	NP_071324.1	Q9H2C0A0A0S2Z4W2B3KTC3
GAN	NM_001377486.1 link	c.-357-2870C>G		intron_variant	Intron 1 of 9		NP_001364415.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
GAN	ENST00000648994.2 link	c.168-48C>G	intron_variant	Intron 1 of 10	NM_022041.4	ENSP00000497351.1	Q9H2C0
GAN	ENST00000648349.2 link	n.168-2870C>G	intron_variant	Intron 1 of 9		ENSP00000498114.1	A0A3B3ITY2
GAN	ENST00000650388.1 link	n.168-5250C>G	intron_variant	Intron 1 of 8		ENSP00000498081.1	A0A0S2Z5G5
GAN	ENST00000674788.1 link	n.293-48C>G	intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.00601

AC:

914

AN:

152108

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.0114

AC XY:

1488

AN XY:

130722

show subpopulations

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.:

AF XY:

0.00872

AC XY:

3080

AN XY:

353228

show subpopulations

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.:

Cov.:

AF XY:

0.00714

AC XY:

531

AN XY:

74416

show subpopulations

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.:

Bravo

AF:

0.00710

Asia WGS

AF:

0.0570

AC:

200

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 08, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

-0.59

CADD

Benign

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

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