13-35194652-C-T

Variant names:

• chr13-35194652-C-T
• rs17051917
• NM_001385012.1:c.4928-1212C>T

Variant summary

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

The NM_001385012.1(NBEA):​c.4928-1212C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 151,910 control chromosomes in the GnomAD database, including 1,508 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 0.13 (1508 hom., cov: 32)
• Consequence: NBEA NM_001385012.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.105
• Publications: 4 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.196 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NBEA	NM_001385012.1	MANE Select	c.4928-1212C>T		intron	N/A	NP_001371941.1	Q5T321
	NBEA	NM_001379245.1		c.4919-1212C>T		intron	N/A	NP_001366174.1
	NBEA	NM_015678.5		c.4928-1212C>T		intron	N/A	NP_056493.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NBEA	ENST00000379939.7	TSL:5 MANE Select	c.4928-1212C>T		intron	N/A	ENSP00000369271.2	Q5T321
	NBEA	ENST00000400445.8	TSL:5	c.4928-1212C>T		intron	N/A	ENSP00000383295.3	Q8NFP9-1
	NBEA	ENST00000688626.1		c.2774-1212C>T		intron	N/A	ENSP00000509239.1	A0A8I5QKR1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19777 AN: 151792 Hom.: 1506 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.0732

Gnomad ASJ AF: 0.0972

Gnomad EAS AF: 0.0634

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.130 AC: 19807 AN: 151910 Hom.: 1508 Cov.: 32 AF XY: 0.132 AC XY: 9783 AN XY: 74228

African (AFR) AF: 0.199 AC: 8270 AN: 41462

American (AMR) AF: 0.0730 AC: 1115 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0972 AC: 337 AN: 3466

East Asian (EAS) AF: 0.0640 AC: 330 AN: 5158

South Asian (SAS) AF: 0.182 AC: 878 AN: 4812

European-Finnish (FIN) AF: 0.143 AC: 1499 AN: 10516

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 6976 AN: 67916

Other (OTH) AF: 0.115 AC: 243 AN: 2106

Alfa AF: 0.103 Hom.: 1934

Bravo AF: 0.125

Asia WGS AF: 0.127 AC: 440 AN: 3452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	8.2
DANN	Benign	0.59
PhyloP100		0.10
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: rs17051917; hg19: chr13-35768789;