13-35031555-T-C

Variant names:

• chr13-35031555-T-C
• rs9315329
• NM_001385012.1:c.295-9378T>C

Variant summary

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

The NM_001385012.1(NBEA):​c.295-9378T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.917 in 151,438 control chromosomes in the GnomAD database, including 64,356 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 0.92 (64356 hom., cov: 31)
• Consequence: NBEA NM_001385012.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.763
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.985 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NBEA	NM_001385012.1	MANE Select	c.295-9378T>C		intron	N/A	NP_001371941.1
	NBEA	NM_001379245.1		c.295-9378T>C		intron	N/A	NP_001366174.1
	NBEA	NM_015678.5		c.295-9378T>C		intron	N/A	NP_056493.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NBEA	ENST00000379939.7	TSL:5 MANE Select	c.295-9378T>C		intron	N/A	ENSP00000369271.2
	NBEA	ENST00000400445.8	TSL:5	c.295-9378T>C		intron	N/A	ENSP00000383295.3
	NBEA	ENST00000691351.1		c.295-9378T>C		intron	N/A	ENSP00000509284.1

Frequencies

GnomAD3 genomes AF: 0.917 AC: 138790 AN: 151320 Hom.: 64329 Cov.: 31

Gnomad AFR AF: 0.773

Gnomad AMI AF: 0.997

Gnomad AMR AF: 0.910

Gnomad ASJ AF: 0.983

Gnomad EAS AF: 0.854

Gnomad SAS AF: 0.956

Gnomad FIN AF: 0.999

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.991

Gnomad OTH AF: 0.935

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

GnomAD4 genome AF: 0.917 AC: 138871 AN: 151438 Hom.: 64356 Cov.: 31 AF XY: 0.916 AC XY: 67828 AN XY: 74028

African (AFR) AF: 0.773 AC: 32022 AN: 41412

American (AMR) AF: 0.910 AC: 13804 AN: 15176

Ashkenazi Jewish (ASJ) AF: 0.983 AC: 3394 AN: 3454

East Asian (EAS) AF: 0.854 AC: 4390 AN: 5140

South Asian (SAS) AF: 0.955 AC: 4607 AN: 4824

European-Finnish (FIN) AF: 0.999 AC: 10602 AN: 10612

Middle Eastern (MID) AF: 0.925 AC: 272 AN: 294

European-Non Finnish (NFE) AF: 0.991 AC: 66911 AN: 67518

Other (OTH) AF: 0.935 AC: 1960 AN: 2096

Alfa AF: 0.948 Hom.: 27789

Bravo AF: 0.902

Asia WGS AF: 0.910 AC: 3166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.0
DANN	Benign	0.64
PhyloP100		-0.76
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: rs9315329; hg19: chr13-35605692;