rs17051776

Positions:

• chr13-34966519-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001385012.1(NBEA):​c.294+23405A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0273 in 152,016 control chromosomes in the GnomAD database, including 82 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 0.027 (82 hom., cov: 32)
• Consequence: NBEA NM_001385012.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.598

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NBEA	NM_001385012.1	c.294+23405A>G		intron_variant		ENST00000379939.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NBEA	ENST00000379939.7	c.294+23405A>G		intron_variant		5	NM_001385012.1

Frequencies

GnomAD3 genomes AF: 0.0273 AC: 4148 AN: 151900 Hom.: 82 Cov.: 32

Gnomad AFR AF: 0.0434

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0170

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.0106

Gnomad SAS AF: 0.0752

Gnomad FIN AF: 0.0165

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0205

Gnomad OTH AF: 0.0249

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

GnomAD4 genome AF: 0.0273 AC: 4148 AN: 152016 Hom.: 82 Cov.: 32 AF XY: 0.0276 AC XY: 2048 AN XY: 74312

Gnomad4 AFR AF: 0.0434

Gnomad4 AMR AF: 0.0169

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.0106

Gnomad4 SAS AF: 0.0748

Gnomad4 FIN AF: 0.0165

Gnomad4 NFE AF: 0.0205

Gnomad4 OTH AF: 0.0247

Alfa AF: 0.0233 Hom.: 10

Bravo AF: 0.0255

Asia WGS AF: 0.0430 AC: 151 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	9.5
DANN	Benign	0.83

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

Other links and lift over

dbSNP: rs17051776; hg19: chr13-35540656;