rs10490481

Variant names:

• chr2-15079920-T-G
• rs10490481
• XM_017004317.2:c.*48+57436A>C

Variant summary

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

The XM_017004317.2(NBAS):​c.*48+57436A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,230 control chromosomes in the GnomAD database, including 3,784 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 0.14 (3784 hom., cov: 32)
• Consequence: NBAS XM_017004317.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 1 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NBAS	XM_017004317.2	c.*48+57436A>C		intron_variant	Intron 52 of 52		XP_016859806.1
NBAS	XR_007076390.1	n.7015+3945A>C		intron_variant	Intron 53 of 53

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20718 AN: 152112 Hom.: 3757 Cov.: 32

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.0103

Gnomad FIN AF: 0.0207

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00604

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.137 AC: 20793 AN: 152230 Hom.: 3784 Cov.: 32 AF XY: 0.136 AC XY: 10135 AN XY: 74444

African (AFR) AF: 0.413 AC: 17115 AN: 41480

American (AMR) AF: 0.140 AC: 2139 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0173 AC: 60 AN: 3472

East Asian (EAS) AF: 0.108 AC: 563 AN: 5190

South Asian (SAS) AF: 0.0101 AC: 49 AN: 4830

European-Finnish (FIN) AF: 0.0207 AC: 220 AN: 10612

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00604 AC: 411 AN: 68030

Other (OTH) AF: 0.109 AC: 230 AN: 2116

Alfa AF: 0.0640 Hom.: 578

Bravo AF: 0.160

Asia WGS AF: 0.0810 AC: 284 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.24
DANN	Benign	0.66
PhyloP100		-1.3

Splicing

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

Other links and lift over

dbSNP: rs10490481; hg19: chr2-15220044;