NM_001385012.1:c.5648+4367G>A

Variant names:

• chr13-35215546-G-A
• rs9600337
• NM_001385012.1:c.5648+4367G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001385012.1(NBEA):​c.5648+4367G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0439 in 151,640 control chromosomes in the GnomAD database, including 157 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 0.044 (157 hom., cov: 32)
• Consequence: NBEA NM_001385012.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.876
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0559 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.5648+4367G>A		intron	N/A	NP_001371941.1	Q5T321
	NBEA	NM_001379245.1		c.5639+4367G>A		intron	N/A	NP_001366174.1
	NBEA	NM_015678.5		c.5648+4367G>A		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.5648+4367G>A		intron	N/A	ENSP00000369271.2	Q5T321
	NBEA	ENST00000400445.8	TSL:5	c.5648+4367G>A		intron	N/A	ENSP00000383295.3	Q8NFP9-1
	NBEA	ENST00000688626.1		c.3494+4367G>A		intron	N/A	ENSP00000509239.1	A0A8I5QKR1

Frequencies

GnomAD3 genomes AF: 0.0439 AC: 6651 AN: 151520 Hom.: 157 Cov.: 32

Gnomad AFR AF: 0.0578

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.0175

Gnomad ASJ AF: 0.0465

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0383

Gnomad FIN AF: 0.0350

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0452

Gnomad OTH AF: 0.0336

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

GnomAD4 genome AF: 0.0439 AC: 6661 AN: 151640 Hom.: 157 Cov.: 32 AF XY: 0.0428 AC XY: 3169 AN XY: 74110

African (AFR) AF: 0.0579 AC: 2400 AN: 41480

American (AMR) AF: 0.0175 AC: 266 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.0465 AC: 161 AN: 3464

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5170

South Asian (SAS) AF: 0.0388 AC: 187 AN: 4820

European-Finnish (FIN) AF: 0.0350 AC: 369 AN: 10554

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0452 AC: 3056 AN: 67654

Other (OTH) AF: 0.0337 AC: 71 AN: 2104

Alfa AF: 0.0443 Hom.: 113

Bravo AF: 0.0429

Asia WGS AF: 0.0280 AC: 98 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.058
DANN	Benign	0.18
PhyloP100		-0.88
Mutation Taster		=100/0	polymorphism

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: rs9600337; hg19: chr13-35789683;