20-58389308-C-G

Variant names:

• chr20-58389308-C-G
• rs753958893
• NM_004738.5:c.-152C>G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_004738.5(VAPB):​c.-152C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000607 in 708,810 control chromosomes in the GnomAD database, including 3 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 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000068 (3 hom.)
• Consequence: VAPB NM_004738.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0930

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BS2: High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VAPB	NM_004738.5	c.-152C>G		5_prime_UTR_variant	Exon 1 of 6	ENST00000475243.6	NP_004729.1
VAPB	NM_001195677.2	c.-152C>G		5_prime_UTR_variant	Exon 1 of 3		NP_001182606.1
VAPB	NR_036633.2	n.80C>G		non_coding_transcript_exon_variant	Exon 1 of 4
VAPB	XR_001754433.3	n.80C>G		non_coding_transcript_exon_variant	Exon 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VAPB	ENST00000475243	c.-152C>G		5_prime_UTR_variant	Exon 1 of 6	1	NM_004738.5	ENSP00000417175.1
VAPB	ENST00000395802.7	c.-152C>G		upstream_gene_variant		1		ENSP00000379147.3
VAPB	ENST00000265619.6	n.-67C>G		upstream_gene_variant		2
VAPB	ENST00000520497.1	n.-152C>G		upstream_gene_variant		2		ENSP00000430426.1

Frequencies

GnomAD3 genomes AF: 0.0000330 AC: 5 AN: 151680 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000284

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000639 AC: 8 AN: 125196 Hom.: 0 AF XY: 0.0000728 AC XY: 5 AN XY: 68688

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000484

Gnomad FIN exome AF: 0.000290

Gnomad NFE exome AF: 0.0000642

Gnomad OTH exome AF: 0.000270

GnomAD4 exome AF: 0.0000682 AC: 38 AN: 557130 Hom.: 3 Cov.: 7 AF XY: 0.0000804 AC XY: 24 AN XY: 298550

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000323

Gnomad4 FIN exome AF: 0.000666

Gnomad4 NFE exome AF: 0.0000317

Gnomad4 OTH exome AF: 0.000108

GnomAD4 genome AF: 0.0000330 AC: 5 AN: 151680 Hom.: 0 Cov.: 33 AF XY: 0.0000405 AC XY: 3 AN XY: 74092

Gnomad4 AFR AF: 0.0000242

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000284

Gnomad4 NFE AF: 0.0000148

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000302

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	14
DANN	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs753958893; hg19: chr20-56964364;