NM_001385012.1:c.1239+30A>T

Variant names:

• chr13-35058893-A-T
• rs17775456
• NM_001385012.1:c.1239+30A>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.1239+30A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0587 in 1,534,536 control chromosomes in the GnomAD database, including 3,036 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 0.046 (239 hom., cov: 32)
  • Exomes 𝑓: 0.060 (2797 hom.)
• Consequence: NBEA NM_001385012.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57
• Publications: 3 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 (NFE) allele frequency at 95% confidence interval = 0.0657 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.1239+30A>T		intron	N/A	NP_001371941.1
	NBEA	NM_001379245.1		c.1239+30A>T		intron	N/A	NP_001366174.1
	NBEA	NM_015678.5		c.1239+30A>T		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.1239+30A>T		intron	N/A	ENSP00000369271.2
	NBEA	ENST00000400445.8	TSL:5	c.1239+30A>T		intron	N/A	ENSP00000383295.3
	NBEA	ENST00000691351.1		c.972+8498A>T		intron	N/A	ENSP00000509284.1

Frequencies

GnomAD3 genomes AF: 0.0457 AC: 6949 AN: 152026 Hom.: 239 Cov.: 32

Gnomad AFR AF: 0.0113

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.0307

Gnomad ASJ AF: 0.0681

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0441

Gnomad FIN AF: 0.0675

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0673

Gnomad OTH AF: 0.0446

GnomAD2 exomes AF: 0.0503 AC: 9332 AN: 185548 AF XY: 0.0517

Gnomad AFR exome AF: 0.0121

Gnomad AMR exome AF: 0.0196

Gnomad ASJ exome AF: 0.0644

Gnomad EAS exome AF: 0.000222

Gnomad FIN exome AF: 0.0659

Gnomad NFE exome AF: 0.0677

Gnomad OTH exome AF: 0.0526

GnomAD4 exome AF: 0.0601 AC: 83101 AN: 1382392 Hom.: 2797 Cov.: 24 AF XY: 0.0597 AC XY: 40923 AN XY: 685392

African (AFR) AF: 0.0100 AC: 309 AN: 30764

American (AMR) AF: 0.0213 AC: 763 AN: 35774

Ashkenazi Jewish (ASJ) AF: 0.0639 AC: 1555 AN: 24352

East Asian (EAS) AF: 0.000241 AC: 9 AN: 37284

South Asian (SAS) AF: 0.0489 AC: 3728 AN: 76290

European-Finnish (FIN) AF: 0.0647 AC: 3306 AN: 51120

Middle Eastern (MID) AF: 0.0386 AC: 202 AN: 5232

European-Non Finnish (NFE) AF: 0.0659 AC: 70128 AN: 1064456

Other (OTH) AF: 0.0543 AC: 3101 AN: 57120

GnomAD4 genome AF: 0.0457 AC: 6951 AN: 152144 Hom.: 239 Cov.: 32 AF XY: 0.0452 AC XY: 3359 AN XY: 74390

African (AFR) AF: 0.0113 AC: 468 AN: 41558

American (AMR) AF: 0.0307 AC: 468 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.0681 AC: 236 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.0446 AC: 215 AN: 4826

European-Finnish (FIN) AF: 0.0675 AC: 716 AN: 10602

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0673 AC: 4576 AN: 67958

Other (OTH) AF: 0.0441 AC: 93 AN: 2108

Alfa AF: 0.0281 Hom.: 22

Bravo AF: 0.0406

Asia WGS AF: 0.0130 AC: 45 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.0070
DANN	Benign	0.73
PhyloP100		-1.6
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: rs17775456; hg19: chr13-35633030;