Genetic Variant NBEA:c.5648+4367G>A (chr13-35215546-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_001385012.1(NBEA):c.5648+4367G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0439 in 151,640 control chromosomes in the GnomAD database, including 157 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 0.044 ( 157 hom., cov: 32)

Consequence

NBEA
NM_001385012.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.876

Publications

1 publications found

Variant links:

Genes affected

NBEA (HGNC:7648): (neurobeachin) This gene encodes a member of a large, diverse group of A-kinase anchor proteins that target the activity of protein kinase A to specific subcellular sites by binding to its type II regulatory subunits. Brain-specific expression and coat protein-like membrane recruitment of a highly similar protein in mouse suggest an involvement in neuronal post-Golgi membrane traffic. Mutations in this gene may be associated with a form of autism. This gene and its expression are frequently disrupted in patients with multiple myeloma. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional transcript variants may exist, but their full-length nature has not been determined.[provided by RefSeq, Feb 2011]

NBEA Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
neurodevelopmental disorder with or without early-onset generalized epilepsy
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
syndromic intellectual disability
Inheritance: AD Classification: STRONG Submitted by: Illumina

NBEA 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=-0.95).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NBEA	NM_001385012.1 link	c.5648+4367G>A		intron_variant	Intron 33 of 58	ENST00000379939.7	NP_001371941.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NBEA	ENST00000379939.7 link	c.5648+4367G>A		intron_variant	Intron 33 of 58	5	NM_001385012.1	ENSP00000369271.2		Q5T321

Frequencies

GnomAD3 genomes

AF:

0.0439

AC:

6651

AN:

151520

Hom.:

157

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0578

Gnomad AMI

AF:

0.159

Gnomad AMR

AF:

0.0175

Gnomad ASJ

AF:

0.0465

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0383

Gnomad FIN

AF:

0.0350

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0452

Gnomad OTH

AF:

0.0336

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

GnomAD4 genome

AF:

0.0439

AC:

6661

AN:

151640

Hom.:

157

Cov.:

AF XY:

0.0428

AC XY:

3169

AN XY:

74110

show subpopulations

African (AFR)

AF:

0.0579

AC:

2400

AN:

41480

American (AMR)

AF:

0.0175

AC:

266

AN:

15190

Ashkenazi Jewish (ASJ)

AF:

0.0465

AC:

161

AN:

3464

East Asian (EAS)

AF:

0.000193

AC:

AN:

5170

South Asian (SAS)

AF:

0.0388

AC:

187

AN:

4820

European-Finnish (FIN)

AF:

0.0350

AC:

369

AN:

10554

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0452

AC:

3056

AN:

67654

Other (OTH)

AF:

0.0337

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

333

666

998

1331

1664

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

246

328

410

<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:

0.0443

Hom.:

113

Bravo

AF:

0.0429

Asia WGS

AF:

0.0280

AC:

AN:

3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.058

(source)

DANN

Benign

0.18

PhyloP100

-0.88

Mutation Taster

=100/0

polymorphism

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over