13-35657351-T-G

Variant names:

• chr13-35657351-T-G
• rs20411
• NM_001385012.1:c.8362+1602T>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.8362+1602T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 152,064 control chromosomes in the GnomAD database, including 32,340 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 0.65 (32340 hom., cov: 33)
• Consequence: NBEA NM_001385012.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.207
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NBEA	NM_001385012.1	c.8362+1602T>G		intron_variant	Intron 55 of 58	ENST00000379939.7	NP_001371941.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NBEA	ENST00000379939.7	c.8362+1602T>G		intron_variant	Intron 55 of 58	5	NM_001385012.1	ENSP00000369271.2

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98474 AN: 151946 Hom.: 32321 Cov.: 33

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.619

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.605

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.684

Gnomad OTH AF: 0.669

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

GnomAD4 genome AF: 0.648 AC: 98543 AN: 152064 Hom.: 32340 Cov.: 33 AF XY: 0.643 AC XY: 47823 AN XY: 74324

African (AFR) AF: 0.637 AC: 26427 AN: 41464

American (AMR) AF: 0.619 AC: 9453 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.699 AC: 2427 AN: 3472

East Asian (EAS) AF: 0.299 AC: 1542 AN: 5164

South Asian (SAS) AF: 0.708 AC: 3415 AN: 4824

European-Finnish (FIN) AF: 0.605 AC: 6402 AN: 10576

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.684 AC: 46523 AN: 67982

Other (OTH) AF: 0.669 AC: 1408 AN: 2106

Alfa AF: 0.658 Hom.: 4963

Bravo AF: 0.643

Asia WGS AF: 0.515 AC: 1795 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.1
DANN	Benign	0.56
PhyloP100		-0.21
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: rs20411; hg19: chr13-36231488;