chr13-35507613-A-G

Variant names:

• chr13-35507613-A-G
• rs9530649
• NM_001385012.1:c.6585+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.6585+35077A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,076 control chromosomes in the GnomAD database, including 1,739 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 0.14 (1739 hom., cov: 31)
• Consequence: NBEA NM_001385012.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.524
• Publications: 0 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NBEA	NM_001385012.1	c.6585+35077A>G		intron_variant	Intron 41 of 58	ENST00000379939.7	NP_001371941.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NBEA	ENST00000379939.7	c.6585+35077A>G		intron_variant	Intron 41 of 58	5	NM_001385012.1	ENSP00000369271.2

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21375 AN: 151958 Hom.: 1738 Cov.: 31

Gnomad AFR AF: 0.0967

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.141 AC: 21375 AN: 152076 Hom.: 1739 Cov.: 31 AF XY: 0.144 AC XY: 10725 AN XY: 74322

African (AFR) AF: 0.0967 AC: 4014 AN: 41508

American (AMR) AF: 0.120 AC: 1832 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 478 AN: 3468

East Asian (EAS) AF: 0.450 AC: 2317 AN: 5154

South Asian (SAS) AF: 0.140 AC: 675 AN: 4824

European-Finnish (FIN) AF: 0.162 AC: 1715 AN: 10574

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.145 AC: 9876 AN: 67974

Other (OTH) AF: 0.145 AC: 307 AN: 2110

Alfa AF: 0.141 Hom.: 840

Bravo AF: 0.138

Asia WGS AF: 0.248 AC: 862 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.2
DANN	Benign	0.69
PhyloP100		0.52
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: rs9530649; hg19: chr13-36081750;