Variant chr13-34942906-GCGGGGGCAGCGGTGGTGGCGGCAC-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP3BP6_ModerateBS1BS2

The NM_001385012.1(NBEA):c.99_122delTGGTGGCGGCACCGGGGGCAGCGG(p.Gly34_Gly41del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000089 in 1,483,832 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000086 ( 0 hom. )

Consequence

NBEA
NM_001385012.1 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter U:1B:1

Conservation

PhyloP100: 5.40

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001385012.1

BP6

Variant 13-34942906-GCGGGGGCAGCGGTGGTGGCGGCAC-G is Benign according to our data. Variant chr13-34942906-GCGGGGGCAGCGGTGGTGGCGGCAC-G is described in ClinVar as [Likely_benign]. Clinvar id is 2643738.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000112 (17/151558) while in subpopulation EAS AF= 0.000199 (1/5018). AF 95% confidence interval is 0.0000795. There are 0 homozygotes in gnomad4. There are 10 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High AC in GnomAd4 at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NBEA	NM_001385012.1 link	c.99_122delTGGTGGCGGCACCGGGGGCAGCGG	p.Gly34_Gly41del	disruptive_inframe_deletion	1/59	ENST00000379939.7	NP_001371941.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NBEA	ENST00000379939.7 link	c.99_122delTGGTGGCGGCACCGGGGGCAGCGG	p.Gly34_Gly41del	disruptive_inframe_deletion	1/59	5	NM_001385012.1	ENSP00000369271.2		Q5T321

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

151450

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000199

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000148

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000152

AC:

AN:

105454

Hom.:

AF XY:

0.000209

AC XY:

AN XY:

57286

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.0000519

Gnomad ASJ exome

AF:

0.000275

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000299

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000863

AC:

115

AN:

1332274

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

652938

show subpopulations

Gnomad4 AFR exome

AF:

0.000106

Gnomad4 AMR exome

AF:

0.000165

Gnomad4 ASJ exome

AF:

0.0000966

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000695

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000918

Gnomad4 OTH exome

AF:

0.0000363

GnomAD4 genome

AF:

0.000112

AC:

AN:

151558

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74082

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000199

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000148

Gnomad4 OTH

AF:

0.00

Asia WGS

AF:

0.000290

AC:

AN:

3458

ClinVar

Significance: Likely benign

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

NBEA-related disorder

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 02, 2024

The NBEA c.99_122del24 variant is predicted to result in an in-frame deletion (p.Gly34_Gly41del). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.032% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

NBEA: BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over