2-15509418-C-G

Variant names:

• chr2-15509418-C-G
• rs1978371
• NM_015909.4:c.885+1794G>C

Variant summary

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

The NM_015909.4(NBAS):​c.885+1794G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 151,960 control chromosomes in the GnomAD database, including 27,057 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 0.59 (27057 hom., cov: 32)
• Consequence: NBAS NM_015909.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.882
• Publications: 3 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NBAS	NM_015909.4	c.885+1794G>C		intron_variant	Intron 10 of 51	ENST00000281513.10	NP_056993.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NBAS	ENST00000281513.10	c.885+1794G>C		intron_variant	Intron 10 of 51	1	NM_015909.4	ENSP00000281513.5

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89590 AN: 151842 Hom.: 27035 Cov.: 32

Gnomad AFR AF: 0.626

Gnomad AMI AF: 0.561

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.630

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

GnomAD4 genome AF: 0.590 AC: 89660 AN: 151960 Hom.: 27057 Cov.: 32 AF XY: 0.584 AC XY: 43411 AN XY: 74292

African (AFR) AF: 0.627 AC: 25964 AN: 41430

American (AMR) AF: 0.581 AC: 8883 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.610 AC: 2117 AN: 3472

East Asian (EAS) AF: 0.227 AC: 1172 AN: 5158

South Asian (SAS) AF: 0.535 AC: 2574 AN: 4812

European-Finnish (FIN) AF: 0.521 AC: 5493 AN: 10550

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.610 AC: 41439 AN: 67942

Other (OTH) AF: 0.625 AC: 1320 AN: 2112

Alfa AF: 0.584 Hom.: 3110

Bravo AF: 0.594

Asia WGS AF: 0.402 AC: 1400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.17
DANN	Benign	0.42
PhyloP100		-0.88
Mutation Taster		=100/0	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: rs1978371; hg19: chr2-15649542;