rs2424534

Variant names:

• chr20-23398229-G-A
• rs2424534
• NM_022080.3:c.179-1041C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-23398229-G-A
• chr20-23398229-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

NAPB Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy 107

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NAPB	NM_022080.3	c.179-1041C>T		intron_variant	Intron 2 of 10	ENST00000377026.4	NP_071363.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAPB	ENST00000377026.4	c.179-1041C>T		intron_variant	Intron 2 of 10	1	NM_022080.3	ENSP00000366225.4

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

African (AFR) AF: 0.262 AC: 10869 AN: 41418

American (AMR) AF: 0.341 AC: 5198 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 961 AN: 3472

East Asian (EAS) AF: 0.332 AC: 1711 AN: 5160

South Asian (SAS) AF: 0.276 AC: 1331 AN: 4822

European-Finnish (FIN) AF: 0.297 AC: 3134 AN: 10552

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.308 AC: 20916 AN: 67952

Other (OTH) AF: 0.298 AC: 628 AN: 2108

Alfa AF: 0.235 Hom.: 756

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
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2424534; hg19: chr20-23378866;