rs762904814

Variant names:

• chr16-81362620-C-A
• rs762904814
• NM_022041.4:c.1086+9C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-81362620-C-A
• chr16-81362620-C-G
• chr16-81362620-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_022041.4(GAN):​c.1086+9C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000853 in 1,173,002 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 8.5e-7 (0 hom.)
• Consequence: GAN NM_022041.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.825
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• giant axonal neuropathy 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAN	NM_022041.4	c.1086+9C>A		intron_variant	Intron 6 of 10	ENST00000648994.2	NP_071324.1
GAN	NM_001377486.1	c.447+9C>A		intron_variant	Intron 5 of 9		NP_001364415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAN	ENST00000648994.2	c.1086+9C>A		intron_variant	Intron 6 of 10		NM_022041.4	ENSP00000497351.1
GAN	ENST00000718305.1	c.1086+9C>A		intron_variant	Intron 6 of 10			ENSP00000520738.1
GAN	ENST00000648349.3	n.*794+9C>A		intron_variant	Intron 5 of 9			ENSP00000498114.1
GAN	ENST00000650388.1	n.*443+9C>A		intron_variant	Intron 4 of 8			ENSP00000498081.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.53e-7 AC: 1 AN: 1173002 Hom.: 0 Cov.: 17 AF XY: 0.00 AC XY: 0 AN XY: 596928

African (AFR) AF: 0.00 AC: 0 AN: 28190

American (AMR) AF: 0.00 AC: 0 AN: 44368

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24316

East Asian (EAS) AF: 0.00 AC: 0 AN: 38440

South Asian (SAS) AF: 0.00 AC: 0 AN: 80502

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53302

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5234

European-Non Finnish (NFE) AF: 0.00000118 AC: 1 AN: 847934

Other (OTH) AF: 0.00 AC: 0 AN: 50716

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.10
DANN	Benign	0.38
PhyloP100		-0.82

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

Other links and lift over

dbSNP: rs762904814; hg19: chr16-81396225;