13-35580829-A-G

Variant names:

• chr13-35580829-A-G
• rs1777670
• NM_001385012.1:c.7036-3069A>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.7036-3069A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.786 in 152,160 control chromosomes in the GnomAD database, including 47,405 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 0.79 (47405 hom., cov: 33)
• Consequence: NBEA NM_001385012.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.216
• Publications: 1 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.835 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.7036-3069A>G		intron	N/A	NP_001371941.1	Q5T321
	NBEA	NM_001379245.1		c.7027-3069A>G		intron	N/A	NP_001366174.1
	NBEA	NM_015678.5		c.7036-3069A>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.7036-3069A>G		intron	N/A	ENSP00000369271.2	Q5T321
	NBEA	ENST00000400445.8	TSL:5	c.7036-3069A>G		intron	N/A	ENSP00000383295.3	Q8NFP9-1
	NBEA	ENST00000688626.1		c.4882-3069A>G		intron	N/A	ENSP00000509239.1	A0A8I5QKR1

Frequencies

GnomAD3 genomes AF: 0.787 AC: 119587 AN: 152042 Hom.: 47381 Cov.: 33

Gnomad AFR AF: 0.702

Gnomad AMI AF: 0.855

Gnomad AMR AF: 0.752

Gnomad ASJ AF: 0.796

Gnomad EAS AF: 0.736

Gnomad SAS AF: 0.760

Gnomad FIN AF: 0.839

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.841

Gnomad OTH AF: 0.802

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

GnomAD4 genome AF: 0.786 AC: 119661 AN: 152160 Hom.: 47405 Cov.: 33 AF XY: 0.785 AC XY: 58411 AN XY: 74396

African (AFR) AF: 0.702 AC: 29103 AN: 41486

American (AMR) AF: 0.752 AC: 11496 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.796 AC: 2765 AN: 3472

East Asian (EAS) AF: 0.737 AC: 3814 AN: 5176

South Asian (SAS) AF: 0.758 AC: 3662 AN: 4828

European-Finnish (FIN) AF: 0.839 AC: 8881 AN: 10580

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.841 AC: 57214 AN: 68014

Other (OTH) AF: 0.802 AC: 1696 AN: 2114

Alfa AF: 0.799 Hom.: 53293

Bravo AF: 0.776

Asia WGS AF: 0.747 AC: 2594 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.0
DANN	Benign	0.86
PhyloP100		-0.22
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: rs1777670; hg19: chr13-36154966;