chr20-58389302-A-ACCC

Variant names:

• chr20-58389302-A-ACCC
• rs546898989
• NM_004738.5:c.-151_-149dupCCC

Variant summary

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

The NM_004738.5(VAPB):​c.-151_-149dupCCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000362 in 400,026 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 0.00032 (0 hom., cov: 27)
  • Exomes 𝑓: 0.00038 (0 hom.)
• Consequence: VAPB NM_004738.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.452

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 GnomAd4 at 41 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VAPB	NM_004738.5	c.-151_-149dupCCC		5_prime_UTR_variant	Exon 1 of 6	ENST00000475243.6	NP_004729.1
VAPB	NM_001195677.2	c.-151_-149dupCCC		5_prime_UTR_variant	Exon 1 of 3		NP_001182606.1
VAPB	NR_036633.2	n.81_83dupCCC		non_coding_transcript_exon_variant	Exon 1 of 4
VAPB	XR_001754433.3	n.81_83dupCCC		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.-151_-149dupCCC		5_prime_UTR_variant	Exon 1 of 6	1	NM_004738.5	ENSP00000417175.1
VAPB	ENST00000395802.7	c.-158_-157insCCC		upstream_gene_variant		1		ENSP00000379147.3

Frequencies

GnomAD3 genomes AF: 0.000319 AC: 41 AN: 128500 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.0000860

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000151

Gnomad ASJ AF: 0.000322

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000288

Gnomad FIN AF: 0.00109

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000436

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000221 AC: 15 AN: 67844 Hom.: 0 AF XY: 0.000212 AC XY: 8 AN XY: 37796

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000768

Gnomad ASJ exome AF: 0.000216

Gnomad EAS exome AF: 0.000201

Gnomad SAS exome AF: 0.0000809

Gnomad FIN exome AF: 0.000402

Gnomad NFE exome AF: 0.000369

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000383 AC: 104 AN: 271526 Hom.: 0 Cov.: 5 AF XY: 0.000408 AC XY: 63 AN XY: 154528

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000223

Gnomad4 ASJ exome AF: 0.000423

Gnomad4 EAS exome AF: 0.000132

Gnomad4 SAS exome AF: 0.000152

Gnomad4 FIN exome AF: 0.000879

Gnomad4 NFE exome AF: 0.000454

Gnomad4 OTH exome AF: 0.000480

GnomAD4 genome AF: 0.000319 AC: 41 AN: 128500 Hom.: 0 Cov.: 27 AF XY: 0.000340 AC XY: 21 AN XY: 61710

Gnomad4 AFR AF: 0.0000860

Gnomad4 AMR AF: 0.000151

Gnomad4 ASJ AF: 0.000322

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000288

Gnomad4 FIN AF: 0.00109

Gnomad4 NFE AF: 0.000436

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: rs546898989; hg19: chr20-56964358;