20-58389301-G-GCC

Position:

• chr20-58389301-G-GCC

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_004738.5(VAPB):​c.-159_-158insCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00057 (0 hom., cov: 27)
  • Exomes 𝑓: 0.00020 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: VAPB NM_004738.5 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• 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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 109 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VAPB	NM_004738.5	c.-159_-158insCC		5_prime_UTR_variant	1/6	ENST00000475243.6	NP_004729.1
VAPB	NM_001195677.2	c.-159_-158insCC		5_prime_UTR_variant	1/3		NP_001182606.1
VAPB	NR_036633.2	n.73_74insCC		non_coding_transcript_exon_variant	1/4
VAPB	XR_001754433.3	n.73_74insCC		non_coding_transcript_exon_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VAPB	ENST00000475243.6	c.-159_-158insCC		5_prime_UTR_variant	1/6	1	NM_004738.5	ENSP00000417175	P1
VAPB	ENST00000395802.7			upstream_gene_variant		1		ENSP00000379147

Frequencies

GnomAD3 genomes AF: 0.00 AC: 75 AN: 132126 Hom.: 0 Cov.: 27 FAILED QC

Gnomad AFR AF: 0.000212

Gnomad AMI AF: 0.00129

Gnomad AMR AF: 0.000142

Gnomad ASJ AF: 0.000309

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000220

Gnomad FIN AF: 0.00174

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000792

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000202 AC: 109 AN: 540450 Hom.: 0 Cov.: 2 AF XY: 0.000179 AC XY: 52 AN XY: 291290

Gnomad4 AFR exome AF: 0.0000818

Gnomad4 AMR exome AF: 0.0000639

Gnomad4 ASJ exome AF: 0.000115

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000147

Gnomad4 FIN exome AF: 0.000269

Gnomad4 NFE exome AF: 0.000231

Gnomad4 OTH exome AF: 0.000367

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000568 AC: 75 AN: 132126 Hom.: 0 Cov.: 27 AF XY: 0.000420 AC XY: 27 AN XY: 64284

Gnomad4 AFR AF: 0.000212

Gnomad4 AMR AF: 0.000142

Gnomad4 ASJ AF: 0.000309

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000220

Gnomad4 FIN AF: 0.00174

Gnomad4 NFE AF: 0.000792

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

Submissions by phenotype

Amyotrophic Lateral Sclerosis, Dominant Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Spinal Muscular Atrophy, Dominant Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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;