chr13-35504290-C-A

Variant names:

• chr13-35504290-C-A
• rs7332116
• NM_001385012.1:c.6585+31754C>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.6585+31754C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,136 control chromosomes in the GnomAD database, including 2,427 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 0.17 (2427 hom., cov: 33)
• Consequence: NBEA NM_001385012.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.906
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.414 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.6585+31754C>A		intron	N/A	NP_001371941.1
	NBEA	NM_001379245.1		c.6576+31754C>A		intron	N/A	NP_001366174.1
	NBEA	NM_015678.5		c.6585+31754C>A		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.6585+31754C>A		intron	N/A	ENSP00000369271.2
	NBEA	ENST00000400445.8	TSL:5	c.6585+31754C>A		intron	N/A	ENSP00000383295.3
	NBEA	ENST00000688626.1		c.4431+31754C>A		intron	N/A	ENSP00000509239.1

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25626 AN: 152018 Hom.: 2426 Cov.: 33

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.168 AC: 25627 AN: 152136 Hom.: 2427 Cov.: 33 AF XY: 0.170 AC XY: 12647 AN XY: 74374

African (AFR) AF: 0.217 AC: 8989 AN: 41512

American (AMR) AF: 0.132 AC: 2017 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 446 AN: 3472

East Asian (EAS) AF: 0.429 AC: 2206 AN: 5148

South Asian (SAS) AF: 0.130 AC: 624 AN: 4818

European-Finnish (FIN) AF: 0.123 AC: 1302 AN: 10598

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9535 AN: 67990

Other (OTH) AF: 0.165 AC: 347 AN: 2108

Alfa AF: 0.152 Hom.: 7394

Bravo AF: 0.174

Asia WGS AF: 0.237 AC: 827 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	1.9
DANN	Benign	0.76
PhyloP100		-0.91
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: rs7332116; hg19: chr13-36078427;