rs2424534

chr20-23398229-G-Achr20-23398229-G-T

Variant summary

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

The NM_022080.3(NAPB):c.179-1041C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 151,942 control chromosomes in the GnomAD database, including 6,769 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 0.30 (6769 hom., cov: 32)
• Consequence: NAPB NM_022080.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117

Genes affected

NAPB (HGNC:15751): (NSF attachment protein beta) This gene encodes a member of the soluble N-ethyl-maleimide-sensitive fusion attachment protein (SNAP) family. SNAP proteins play a critical role in the docking and fusion of vesicles to target membranes as part of the 20S NSF-SNAP-SNARE complex. This gene encodes the SNAP beta isoform which has been shown to be preferentially expressed in brain tissue. The encoded protein also interacts with the GluR2 α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor subunit C-terminus and may play a role as a chaperone in the molecular processing of the AMPA receptor. [provided by RefSeq, Mar 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAPB	NM_022080.3	c.179-1041C>T		intron_variant		ENST00000377026.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAPB	ENST00000377026.4	c.179-1041C>T		intron_variant		1	NM_022080.3	P3

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45199 AN: 151824 Hom.: 6766 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.299

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.298 AC: 45222 AN: 151942 Hom.: 6769 Cov.: 32 AF XY: 0.300 AC XY: 22284 AN XY: 74268

Gnomad4 AFR AF: 0.262

Gnomad4 AMR AF: 0.341

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.276

Gnomad4 FIN AF: 0.297

Gnomad4 NFE AF: 0.308

Gnomad4 OTH AF: 0.298

Alfa AF: 0.233 Hom.: 730

Bravo AF: 0.302

Asia WGS AF: 0.295 AC: 1025 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.2
Dann	Benign	0.30

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: rs2424534; hg19: chr20-23378866;