chr20-58389301-G-GGC

Variant names:

• chr20-58389301-G-GGC
• rs886056808
• NM_004738.5:c.-159_-158insGC

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004738.5(VAPB):​c.-159_-158insGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000757 in 132,156 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000076 (0 hom., cov: 27)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: VAPB NM_004738.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VAPB	NM_004738.5	c.-159_-158insGC		5_prime_UTR_variant	Exon 1 of 6	ENST00000475243.6	NP_004729.1
VAPB	NM_001195677.2	c.-159_-158insGC		5_prime_UTR_variant	Exon 1 of 3		NP_001182606.1
VAPB	NR_036633.2	n.73_74insGC		non_coding_transcript_exon_variant	Exon 1 of 4
VAPB	XR_001754433.3	n.73_74insGC		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.-159_-158insGC		5_prime_UTR_variant	Exon 1 of 6	1	NM_004738.5	ENSP00000417175.1
VAPB	ENST00000395802.7	c.-159_-158insGC		upstream_gene_variant		1		ENSP00000379147.3
VAPB	ENST00000265619.6	n.-74_-73insGC		upstream_gene_variant		2
VAPB	ENST00000520497.1	n.-159_-158insGC		upstream_gene_variant		2		ENSP00000430426.1

Frequencies

GnomAD3 genomes AF: 0.00000757 AC: 1 AN: 132156 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.00

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: 0.000116

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 540534 Hom.: 0 Cov.: 2 AF XY: 0.00 AC XY: 0 AN XY: 291334

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000757 AC: 1 AN: 132156 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 64296

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000116

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs886056808; hg19: chr20-56964357;