Genetic Variant NBEA:c.1239+30A>T (chr13-35058893-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001385012.1(NBEA):c.1239+30A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0587 in 1,534,536 control chromosomes in the GnomAD database, including 3,036 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 0.046 ( 239 hom., cov: 32)

Exomes 𝑓: 0.060 ( 2797 hom. )

Consequence

NBEA
NM_001385012.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.57

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NBEA	NM_001385012.1 link	c.1239+30A>T		intron_variant	Intron 8 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.1239+30A>T		intron_variant	Intron 8 of 58	5	NM_001385012.1	ENSP00000369271.2		Q5T321

Frequencies

GnomAD3 genomes

AF:

0.0457

AC:

6949

AN:

152026

Hom.:

239

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0113

Gnomad AMI

AF:

0.181

Gnomad AMR

AF:

0.0307

Gnomad ASJ

AF:

0.0681

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0441

Gnomad FIN

AF:

0.0675

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0673

Gnomad OTH

AF:

0.0446

GnomAD3 exomes

AF:

0.0503

AC:

9332

AN:

185548

Hom.:

304

AF XY:

0.0517

AC XY:

5153

AN XY:

99648

show subpopulations

Gnomad AFR exome

AF:

0.0121

Gnomad AMR exome

AF:

0.0196

Gnomad ASJ exome

AF:

0.0644

Gnomad EAS exome

AF:

0.000222

Gnomad SAS exome

AF:

0.0517

Gnomad FIN exome

AF:

0.0659

Gnomad NFE exome

AF:

0.0677

Gnomad OTH exome

AF:

0.0526

GnomAD4 exome

AF:

0.0601

AC:

83101

AN:

1382392

Hom.:

2797

Cov.:

AF XY:

0.0597

AC XY:

40923

AN XY:

685392

show subpopulations

Gnomad4 AFR exome

AF:

0.0100

Gnomad4 AMR exome

AF:

0.0213

Gnomad4 ASJ exome

AF:

0.0639

Gnomad4 EAS exome

AF:

0.000241

Gnomad4 SAS exome

AF:

0.0489

Gnomad4 FIN exome

AF:

0.0647

Gnomad4 NFE exome

AF:

0.0659

Gnomad4 OTH exome

AF:

0.0543

GnomAD4 genome

AF:

0.0457

AC:

6951

AN:

152144

Hom.:

239

Cov.:

AF XY:

0.0452

AC XY:

3359

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.0113

Gnomad4 AMR

AF:

0.0307

Gnomad4 ASJ

AF:

0.0681

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0446

Gnomad4 FIN

AF:

0.0675

Gnomad4 NFE

AF:

0.0673

Gnomad4 OTH

AF:

0.0441

Alfa

AF:

0.0281

Hom.:

Bravo

AF:

0.0406

Asia WGS

AF:

0.0130

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.0070

DANN

Benign

0.73

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over