chr13-35031555-T-C

Position:

• chr13-35031555-T-C

Variant summary

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

The NM_001385012.1(NBEA):​c.295-9378T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.917 in 151,438 control chromosomes in the GnomAD database, including 64,356 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 0.92 (64356 hom., cov: 31)
• Consequence: NBEA NM_001385012.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.763

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.985 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NBEA	NM_001385012.1	c.295-9378T>C		intron_variant		ENST00000379939.7	NP_001371941.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NBEA	ENST00000379939.7	c.295-9378T>C		intron_variant		5	NM_001385012.1	ENSP00000369271

Frequencies

GnomAD3 genomes AF: 0.917 AC: 138790 AN: 151320 Hom.: 64329 Cov.: 31

Gnomad AFR AF: 0.773

Gnomad AMI AF: 0.997

Gnomad AMR AF: 0.910

Gnomad ASJ AF: 0.983

Gnomad EAS AF: 0.854

Gnomad SAS AF: 0.956

Gnomad FIN AF: 0.999

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.991

Gnomad OTH AF: 0.935

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

GnomAD4 genome AF: 0.917 AC: 138871 AN: 151438 Hom.: 64356 Cov.: 31 AF XY: 0.916 AC XY: 67828 AN XY: 74028

Gnomad4 AFR AF: 0.773

Gnomad4 AMR AF: 0.910

Gnomad4 ASJ AF: 0.983

Gnomad4 EAS AF: 0.854

Gnomad4 SAS AF: 0.955

Gnomad4 FIN AF: 0.999

Gnomad4 NFE AF: 0.991

Gnomad4 OTH AF: 0.935

Alfa AF: 0.950 Hom.: 22332

Bravo AF: 0.902

Asia WGS AF: 0.910 AC: 3166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.0
DANN	Benign	0.64

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: rs9315329; hg19: chr13-35605692;