rs1197850

Variant names:

• chr13-35356607-T-G
• rs1197850
• NM_001385012.1:c.6179+4284T>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.6179+4284T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 152,100 control chromosomes in the GnomAD database, including 7,097 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 0.27 (7097 hom., cov: 32)
• Consequence: NBEA NM_001385012.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NBEA	NM_001385012.1	c.6179+4284T>G		intron_variant	Intron 38 of 58	ENST00000379939.7	NP_001371941.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NBEA	ENST00000379939.7	c.6179+4284T>G		intron_variant	Intron 38 of 58	5	NM_001385012.1	ENSP00000369271.2

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41450 AN: 151982 Hom.: 7082 Cov.: 32

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.197

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.273 AC: 41514 AN: 152100 Hom.: 7097 Cov.: 32 AF XY: 0.270 AC XY: 20061 AN XY: 74338

African (AFR) AF: 0.487 AC: 20185 AN: 41452

American (AMR) AF: 0.202 AC: 3082 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 760 AN: 3472

East Asian (EAS) AF: 0.219 AC: 1134 AN: 5168

South Asian (SAS) AF: 0.257 AC: 1238 AN: 4818

European-Finnish (FIN) AF: 0.157 AC: 1665 AN: 10600

Middle Eastern (MID) AF: 0.188 AC: 55 AN: 292

European-Non Finnish (NFE) AF: 0.185 AC: 12568 AN: 67998

Other (OTH) AF: 0.251 AC: 531 AN: 2112

Alfa AF: 0.200 Hom.: 3752

Bravo AF: 0.286

Asia WGS AF: 0.259 AC: 900 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.80
PhyloP100		0.079
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: rs1197850; hg19: chr13-35930744;