NM_001385012.1:c.7618-5443C>A

Variant names:

• chr13-35640426-C-A
• rs7327540
• NM_001385012.1:c.7618-5443C>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.7618-5443C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 152,064 control chromosomes in the GnomAD database, including 17,612 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 0.47 (17612 hom., cov: 32)
• Consequence: NBEA NM_001385012.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.901
• Publications: 5 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 = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NBEA	NM_001385012.1	c.7618-5443C>A		intron_variant	Intron 49 of 58	ENST00000379939.7	NP_001371941.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NBEA	ENST00000379939.7	c.7618-5443C>A		intron_variant	Intron 49 of 58	5	NM_001385012.1	ENSP00000369271.2

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71885 AN: 151944 Hom.: 17587 Cov.: 32

Gnomad AFR AF: 0.579

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.442

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

GnomAD4 genome AF: 0.473 AC: 71955 AN: 152064 Hom.: 17612 Cov.: 32 AF XY: 0.474 AC XY: 35237 AN XY: 74322

African (AFR) AF: 0.579 AC: 24030 AN: 41498

American (AMR) AF: 0.348 AC: 5309 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 1543 AN: 3466

East Asian (EAS) AF: 0.560 AC: 2893 AN: 5166

South Asian (SAS) AF: 0.527 AC: 2543 AN: 4822

European-Finnish (FIN) AF: 0.462 AC: 4886 AN: 10580

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.429 AC: 29170 AN: 67950

Other (OTH) AF: 0.447 AC: 944 AN: 2112

Alfa AF: 0.438 Hom.: 57848

Bravo AF: 0.469

Asia WGS AF: 0.560 AC: 1948 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	0.19
DANN	Benign	0.43
PhyloP100		-0.90
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: rs7327540; hg19: chr13-36214563;