rs9530649

chr13-35507613-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001385012.1(NBEA):c.6585+35077A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,076 control chromosomes in the GnomAD database, including 1,739 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 0.14 (1739 hom., cov: 31)
• Consequence: NBEA NM_001385012.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.524

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NBEA	NM_001385012.1	c.6585+35077A>G		intron_variant		ENST00000379939.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NBEA	ENST00000379939.7	c.6585+35077A>G		intron_variant		5	NM_001385012.1

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21375 AN: 151958 Hom.: 1738 Cov.: 31

Gnomad AFR AF: 0.0967

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.141 AC: 21375 AN: 152076 Hom.: 1739 Cov.: 31 AF XY: 0.144 AC XY: 10725 AN XY: 74322

Gnomad4 AFR AF: 0.0967

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.450

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.145

Gnomad4 OTH AF: 0.145

Alfa AF: 0.141 Hom.: 753

Bravo AF: 0.138

Asia WGS AF: 0.248 AC: 862 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	5.2
Dann	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs9530649; hg19: chr13-36081750;