chr13-35515400-A-G

Variant names:

• chr13-35515400-A-G
• rs981386
• NM_001385012.1:c.6586-35077A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385012.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NBEA	NM_001385012.1	MANE Select	c.6586-35077A>G		intron	N/A	NP_001371941.1	Q5T321
	NBEA	NM_001379245.1		c.6577-35077A>G		intron	N/A	NP_001366174.1
	NBEA	NM_015678.5		c.6586-35077A>G		intron	N/A	NP_056493.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NBEA	ENST00000379939.7	TSL:5 MANE Select	c.6586-35077A>G		intron	N/A	ENSP00000369271.2	Q5T321
	NBEA	ENST00000400445.8	TSL:5	c.6586-35077A>G		intron	N/A	ENSP00000383295.3	Q8NFP9-1
	NBEA	ENST00000688626.1		c.4432-35077A>G		intron	N/A	ENSP00000509239.1	A0A8I5QKR1

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

African (AFR) AF: 0.844 AC: 35055 AN: 41528

American (AMR) AF: 0.878 AC: 13423 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.863 AC: 2994 AN: 3470

East Asian (EAS) AF: 0.547 AC: 2816 AN: 5148

South Asian (SAS) AF: 0.859 AC: 4147 AN: 4828

European-Finnish (FIN) AF: 0.878 AC: 9312 AN: 10604

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.860 AC: 58493 AN: 68004

Other (OTH) AF: 0.843 AC: 1777 AN: 2108

Alfa AF: 0.857 Hom.: 91704

Bravo AF: 0.844

Asia WGS AF: 0.746 AC: 2596 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	8.8
DANN	Benign	0.79
PhyloP100		-0.0090
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs981386; hg19: chr13-36089537;