rs981386

Positions:

• chr13-35515400-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.6586-35077A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.848 in 152,190 control chromosomes in the GnomAD database, including 54,940 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 0.85 (54940 hom., cov: 32)
• Consequence: NBEA NM_001385012.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900

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=-0.6).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NBEA	NM_001385012.1	c.6586-35077A>G		intron_variant		ENST00000379939.7	NP_001371941.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NBEA	ENST00000379939.7	c.6586-35077A>G		intron_variant		5	NM_001385012.1	ENSP00000369271

Frequencies

GnomAD3 genomes AF: 0.848 AC: 128945 AN: 152072 Hom.: 54879 Cov.: 32

Gnomad AFR AF: 0.844

Gnomad AMI AF: 0.863

Gnomad AMR AF: 0.877

Gnomad ASJ AF: 0.863

Gnomad EAS AF: 0.547

Gnomad SAS AF: 0.858

Gnomad FIN AF: 0.878

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.860

Gnomad OTH AF: 0.843

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

GnomAD4 genome AF: 0.848 AC: 129061 AN: 152190 Hom.: 54940 Cov.: 32 AF XY: 0.847 AC XY: 63046 AN XY: 74398

Gnomad4 AFR AF: 0.844

Gnomad4 AMR AF: 0.878

Gnomad4 ASJ AF: 0.863

Gnomad4 EAS AF: 0.547

Gnomad4 SAS AF: 0.859

Gnomad4 FIN AF: 0.878

Gnomad4 NFE AF: 0.860

Gnomad4 OTH AF: 0.843

Alfa AF: 0.857 Hom.: 71887

Bravo AF: 0.844

Asia WGS AF: 0.746 AC: 2596 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	8.8
DANN	Benign	0.79

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: rs981386; hg19: chr13-36089537;