Variant chr13-34942660-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_001385012.1(NBEA):c.-161C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00162 in 408,456 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.0017 ( 4 hom., cov: 31)

Exomes 𝑓: 0.0016 ( 0 hom. )

Consequence

NBEA
NM_001385012.1 5_prime_UTR

Scores

Splicing: ADA: 0.002176

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: -0.129

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00168 (255/151564) while in subpopulation NFE AF= 0.00207 (140/67776). AF 95% confidence interval is 0.00179. There are 4 homozygotes in gnomad4. There are 101 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High AC in GnomAd4 at 255 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NBEA	NM_001385012.1 linkuse as main transcript	c.-161C>T		5_prime_UTR_variant	1/59	ENST00000379939.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NBEA	ENST00000379939.7 linkuse as main transcript	c.-161C>T		5_prime_UTR_variant	1/59	5	NM_001385012.1

Frequencies

GnomAD3 genomes

AF:

0.00168

AC:

255

AN:

151458

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000411

Gnomad AMI

AF:

0.104

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00207

Gnomad OTH

AF:

0.000479

GnomAD4 exome

AF:

0.00158

AC:

406

AN:

256892

Hom.:

Cov.:

AF XY:

0.00145

AC XY:

188

AN XY:

129880

show subpopulations

Gnomad4 AFR exome

AF:

0.000616

Gnomad4 AMR exome

AF:

0.000169

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000636

Gnomad4 NFE exome

AF:

0.00209

Gnomad4 OTH exome

AF:

0.000877

GnomAD4 genome

AF:

0.00168

AC:

255

AN:

151564

Hom.:

Cov.:

AF XY:

0.00136

AC XY:

101

AN XY:

74098

show subpopulations

Gnomad4 AFR

AF:

0.000410

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00207

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.00122

Hom.:

Bravo

AF:

0.00202

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Thrombocytopenia;C1458140:Abnormal bleeding

Uncertain:1

Uncertain significance, no assertion criteria provided

research

Birmingham Platelet Group; University of Birmingham

May 01, 2020

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.92

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0022

dbscSNV1_RF

Benign

0.054

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over