rs2031011

Variant names:

• chr2-15408266-T-C
• rs2031011
• NM_015909.4:c.2938-5965A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015909.4(NBAS):​c.2938-5965A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 152,104 control chromosomes in the GnomAD database, including 26,776 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 0.55 (26776 hom., cov: 32)
• Consequence: NBAS NM_015909.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.610
• Publications: 7 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NBAS	NM_015909.4	c.2938-5965A>G		intron_variant	Intron 25 of 51	ENST00000281513.10	NP_056993.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NBAS	ENST00000281513.10	c.2938-5965A>G		intron_variant	Intron 25 of 51	1	NM_015909.4	ENSP00000281513.5

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84268 AN: 151986 Hom.: 26791 Cov.: 32

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.848

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.766

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.725

Gnomad OTH AF: 0.621

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

GnomAD4 genome AF: 0.554 AC: 84267 AN: 152104 Hom.: 26776 Cov.: 32 AF XY: 0.549 AC XY: 40822 AN XY: 74374

African (AFR) AF: 0.273 AC: 11316 AN: 41490

American (AMR) AF: 0.596 AC: 9107 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.766 AC: 2657 AN: 3470

East Asian (EAS) AF: 0.163 AC: 841 AN: 5174

South Asian (SAS) AF: 0.479 AC: 2309 AN: 4824

European-Finnish (FIN) AF: 0.612 AC: 6475 AN: 10582

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.725 AC: 49297 AN: 67964

Other (OTH) AF: 0.614 AC: 1295 AN: 2108

Alfa AF: 0.677 Hom.: 61551

Bravo AF: 0.540

Asia WGS AF: 0.340 AC: 1183 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	11
DANN	Benign	0.93
PhyloP100		0.61
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2031011; hg19: chr2-15548390;