16-81366471-A-G

Variant summary

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

The NM_022041.4(GAN):c.1502+993A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 152,058 control chromosomes in the GnomAD database, including 31,679 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 0.64 (31679 hom., cov: 32)
• Consequence: GAN NM_022041.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAN	NM_022041.4	c.1502+993A>G		intron_variant		ENST00000648994.2
GAN	NM_001377486.1	c.863+993A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAN	ENST00000648994.2	c.1502+993A>G		intron_variant			NM_022041.4	P1
GAN	ENST00000648349.2	c.*1210+993A>G		intron_variant, NMD_transcript_variant
GAN	ENST00000650388.1	c.*859+993A>G		intron_variant, NMD_transcript_variant
GAN	ENST00000567335.1	n.60+993A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.645 AC: 98019 AN: 151940 Hom.: 31665 Cov.: 32

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.699

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.651

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.694

Gnomad FIN AF: 0.541

Gnomad MID AF: 0.656

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.636

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.645 AC: 98068 AN: 152058 Hom.: 31679 Cov.: 32 AF XY: 0.643 AC XY: 47810 AN XY: 74308

Gnomad4 AFR AF: 0.670

Gnomad4 AMR AF: 0.669

Gnomad4 ASJ AF: 0.651

Gnomad4 EAS AF: 0.751

Gnomad4 SAS AF: 0.693

Gnomad4 FIN AF: 0.541

Gnomad4 NFE AF: 0.628

Gnomad4 OTH AF: 0.632

Alfa AF: 0.628 Hom.: 13777

Bravo AF: 0.660

Asia WGS AF: 0.669 AC: 2327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.084
Dann	Benign	0.36

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: rs1037973; hg19: chr16-81400076;