rs7327540

chr13-35640426-C-Achr13-35640426-C-G

Variant summary

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

The NM_001385012.1(NBEA):c.7618-5443C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 152,064 control chromosomes in the GnomAD database, including 17,612 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 0.47 (17612 hom., cov: 32)
• Consequence: NBEA NM_001385012.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.901

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NBEA	NM_001385012.1	c.7618-5443C>A		intron_variant		ENST00000379939.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NBEA	ENST00000379939.7	c.7618-5443C>A		intron_variant		5	NM_001385012.1

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71885 AN: 151944 Hom.: 17587 Cov.: 32

Gnomad AFR AF: 0.579

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.442

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

GnomAD4 genome AF: 0.473 AC: 71955 AN: 152064 Hom.: 17612 Cov.: 32 AF XY: 0.474 AC XY: 35237 AN XY: 74322

Gnomad4 AFR AF: 0.579

Gnomad4 AMR AF: 0.348

Gnomad4 ASJ AF: 0.445

Gnomad4 EAS AF: 0.560

Gnomad4 SAS AF: 0.527

Gnomad4 FIN AF: 0.462

Gnomad4 NFE AF: 0.429

Gnomad4 OTH AF: 0.447

Alfa AF: 0.429 Hom.: 23880

Bravo AF: 0.469

Asia WGS AF: 0.560 AC: 1948 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.19
Dann	Benign	0.43

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: rs7327540; hg19: chr13-36214563;