dbSNP rs2424534: NAPB:c.179-1041C>T (chr20-23398229-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001283018.2(NAPB):c.179-1029C>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_001283018.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.117

Publications

7 publications found

Variant links:

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

NAPB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001283018.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NAPB	NM_022080.3	MANE Select	c.179-1041C>T	intron	N/A	NP_071363.1
NAPB	NM_001283018.2		c.179-1029C>T	intron	N/A	NP_001269947.1
NAPB	NM_001283020.2		c.179-3044C>T	intron	N/A	NP_001269949.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NAPB	ENST00000377026.4	TSL:1 MANE Select	c.179-1041C>T	intron	N/A	ENSP00000366225.4
NAPB	ENST00000398425.7	TSL:1	c.-57-1041C>T	intron	N/A	ENSP00000381459.3
NAPB	ENST00000617876.4	TSL:2	c.179-1029C>T	intron	N/A	ENSP00000482826.1

Frequencies

GnomAD3 genomes

AF:

0.298

AC:

45199

AN:

151824

Hom.:

6766

Cov.:

show subpopulations

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.:

AF XY:

0.300

AC XY:

22284

AN XY:

74268

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1641

3282

4922

6563

8204

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

464

928

1392

1856

2320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.2

(source)

DANN

Benign

0.30

PhyloP100

0.12

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over