13-35194652-C-T

Position:

• chr13-35194652-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NBEA	NM_001385012.1	c.4928-1212C>T		intron_variant		ENST00000379939.7	NP_001371941.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NBEA	ENST00000379939.7	c.4928-1212C>T		intron_variant		5	NM_001385012.1	ENSP00000369271.2

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

Gnomad4 AFR AF: 0.199

Gnomad4 AMR AF: 0.0730

Gnomad4 ASJ AF: 0.0972

Gnomad4 EAS AF: 0.0640

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.115

Alfa AF: 0.0977 Hom.: 698

Bravo AF: 0.125

Asia WGS AF: 0.127 AC: 440 AN: 3452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	8.2
DANN	Benign	0.59

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: rs17051917; hg19: chr13-35768789;