rs6026230

Positions:

• chr20-58390228-T-C

Variant summary

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

The ENST00000475243.6(VAPB):​c.58+711T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 151,910 control chromosomes in the GnomAD database, including 8,886 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 0.33 (8881 hom., cov: 31)
  • Exomes 𝑓: 0.33 (5 hom.)
• Consequence: VAPB ENST00000475243.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.612

Genes affected

VAPB (HGNC:12649): (VAMP associated protein B and C) The protein encoded by this gene is a type IV membrane protein found in plasma and intracellular vesicle membranes. The encoded protein is found as a homodimer and as a heterodimer with VAPA. This protein also can interact with VAMP1 and VAMP2 and may be involved in vesicle trafficking. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VAPB	NM_004738.5	c.58+711T>C		intron_variant		ENST00000475243.6	NP_004729.1
VAPB	NM_001195677.2	c.58+711T>C		intron_variant			NP_001182606.1
VAPB	NR_036633.2	n.289+711T>C		intron_variant, non_coding_transcript_variant
VAPB	XR_001754433.3	n.289+711T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VAPB	ENST00000475243.6	c.58+711T>C		intron_variant		1	NM_004738.5	ENSP00000417175	P1
VAPB	ENST00000395802.7	c.58+711T>C		intron_variant		1		ENSP00000379147
VAPB	ENST00000265619.6	n.244T>C		non_coding_transcript_exon_variant	2/6	2
VAPB	ENST00000520497.1	c.58+711T>C		intron_variant, NMD_transcript_variant		2		ENSP00000430426

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49815 AN: 151732 Hom.: 8859 Cov.: 31

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.308

GnomAD4 exome AF: 0.333 AC: 20 AN: 60 Hom.: 5 Cov.: 0 AF XY: 0.361 AC XY: 13 AN XY: 36

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.500

Gnomad4 SAS exome AF: 0.167

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.310

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.329 AC: 49886 AN: 151850 Hom.: 8881 Cov.: 31 AF XY: 0.325 AC XY: 24142 AN XY: 74210

Gnomad4 AFR AF: 0.472

Gnomad4 AMR AF: 0.306

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.274

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.271

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.307

Alfa AF: 0.288 Hom.: 5081

Bravo AF: 0.339

Asia WGS AF: 0.219 AC: 763 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.9
DANN	Benign	0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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: rs6026230; hg19: chr20-56965284;