chr2-15478280-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_015909.4(NBAS):c.1093G>C(p.Asp365His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 1,610,118 control chromosomes in the GnomAD database, including 101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D365E) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0077 ( 9 hom., cov: 32)

Exomes 𝑓: 0.011 ( 92 hom. )

Consequence

NBAS
NM_015909.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 3.32

Publications

10 publications found

Variant links:

Genes affected

NBAS (HGNC:15625): (NBAS subunit of NRZ tethering complex) This gene encodes a protein with two leucine zipper domains, a ribosomal protein S14 signature domain and a Sec39 like domain. The protein is thought to be involved in Golgi-to-ER transport. Mutations in this gene are associated with short stature, optic nerve atrophy, and Pelger-Huet anomaly. [provided by RefSeq, Oct 2012]

NBAS Gene-Disease associations (from GenCC):

infantile liver failure syndrome 2
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
short stature-optic atrophy-Pelger-Huët anomaly syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Illumina, Labcorp Genetics (formerly Invitae), G2P

NBAS links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008595169).

BP6

Variant 2-15478280-C-G is Benign according to our data. Variant chr2-15478280-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 446082.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00769 (1170/152238) while in subpopulation NFE AF = 0.0132 (900/68012). AF 95% confidence interval is 0.0125. There are 9 homozygotes in GnomAd4. There are 579 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NBAS	NM_015909.4 link	c.1093G>C	p.Asp365His	missense_variant	Exon 13 of 52	ENST00000281513.10	NP_056993.2	A2RRP1-1G1UI26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NBAS	ENST00000281513.10 link	c.1093G>C	p.Asp365His	missense_variant	Exon 13 of 52	1	NM_015909.4	ENSP00000281513.5		A2RRP1-1

Frequencies

GnomAD3 genomes

AF:

0.00771

AC:

1173

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00191

Gnomad AMI

AF:

0.0417

Gnomad AMR

AF:

0.00400

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.00547

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0132

Gnomad OTH

AF:

0.00670

GnomAD2 exomes

AF:

0.00791

AC:

1984

AN:

250708

AF XY:

0.00783

show subpopulations

Gnomad AFR exome

AF:

0.00271

Gnomad AMR exome

AF:

0.00278

Gnomad ASJ exome

AF:

0.00209

Gnomad EAS exome

AF:

0.0000545

Gnomad FIN exome

AF:

0.00623

Gnomad NFE exome

AF:

0.0132

Gnomad OTH exome

AF:

0.00589

GnomAD4 exome

AF:

0.0107

AC:

15611

AN:

1457880

Hom.:

Cov.:

AF XY:

0.0106

AC XY:

7712

AN XY:

725596

show subpopulations

African (AFR)

AF:

0.00177

AC:

AN:

33396

American (AMR)

AF:

0.00318

AC:

142

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00245

AC:

AN:

26100

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39632

South Asian (SAS)

AF:

0.00533

AC:

459

AN:

86164

European-Finnish (FIN)

AF:

0.00661

AC:

352

AN:

53266

Middle Eastern (MID)

AF:

0.00104

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.0127

AC:

14025

AN:

1108596

Other (OTH)

AF:

0.00835

AC:

503

AN:

60252

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

671

1343

2014

2686

3357

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

502

1004

1506

2008

2510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00769

AC:

1170

AN:

152238

Hom.:

Cov.:

AF XY:

0.00778

AC XY:

579

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.00190

AC:

AN:

41546

American (AMR)

AF:

0.00392

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00332

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00547

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0132

AC:

900

AN:

68012

Other (OTH)

AF:

0.00616

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

128

193

257

321

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00995

Hom.:

Bravo

AF:

0.00759

TwinsUK

AF:

0.0154

AC:

ALSPAC

AF:

0.0153

AC:

ESP6500AA

AF:

0.00295

AC:

ESP6500EA

AF:

0.0130

AC:

112

ExAC

AF:

0.00859

AC:

1043

Asia WGS

AF:

0.00144

AC:

AN:

3476

EpiCase

AF:

0.0108

EpiControl

AF:

0.0114

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

NBAS: BP4, BS1, BS2 -

Sep 15, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.55

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.92

MetaRNN

Benign

0.0086

MetaSVM

Benign

-0.53

MutationAssessor

Uncertain

2.1

PhyloP100

3.3

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-3.6

REVEL

Benign

0.21

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.0080

Polyphen

0.97

Vest4

0.73

MVP

0.76

MPC

0.19

ClinPred

0.032

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.51

gMVP

0.52

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over