rs2183863

Positions:

• chr9-77218543-A-G
• chr9-77218543-A-T

Variant summary

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

The NM_033305.3(VPS13A):​c.755-1411A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 151,784 control chromosomes in the GnomAD database, including 3,360 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 0.20 (3360 hom., cov: 30)
• Consequence: VPS13A NM_033305.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

Genes affected

VPS13A (HGNC:1908): (vacuolar protein sorting 13 homolog A) The protein encoded by this gene may control steps in the cycling of proteins through the trans-Golgi network to endosomes, lysosomes and the plasma membrane. Mutations in this gene cause the autosomal recessive disorder, chorea-acanthocytosis. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS13A	NM_033305.3	c.755-1411A>G		intron_variant		ENST00000360280.8	NP_150648.2
VPS13A	NM_001018037.2	c.755-1411A>G		intron_variant			NP_001018047.1
VPS13A	NM_001018038.3	c.755-1411A>G		intron_variant			NP_001018048.1
VPS13A	NM_015186.4	c.755-1411A>G		intron_variant			NP_056001.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS13A	ENST00000360280.8	c.755-1411A>G		intron_variant		1	NM_033305.3	ENSP00000353422	P4
VPS13A	ENST00000376636.7	c.755-1411A>G		intron_variant		1		ENSP00000365823
VPS13A	ENST00000643348.1	c.755-1411A>G		intron_variant				ENSP00000493592
VPS13A	ENST00000645632.1	c.755-1411A>G		intron_variant				ENSP00000496361	A1

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30959 AN: 151674 Hom.: 3349 Cov.: 30

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.0567

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.204 AC: 31006 AN: 151784 Hom.: 3360 Cov.: 30 AF XY: 0.200 AC XY: 14846 AN XY: 74154

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.0572

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.181

Alfa AF: 0.204 Hom.: 525

Bravo AF: 0.204

Asia WGS AF: 0.139 AC: 486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.32
DANN	Benign	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

Publications

LitVar

Other links and lift over

dbSNP: rs2183863; hg19: chr9-79833459;