rs1518790

Variant names:

• chr2-14837262-T-A
• rs1518790
• ENST00000654007.1:n.857-123967A>T

Variant summary

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

The ENST00000654007.1(ENSG00000287291):​n.857-123967A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 151,788 control chromosomes in the GnomAD database, including 7,124 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 0.29 (7124 hom., cov: 33)
• Consequence: ENSG00000287291 ENST00000654007.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.413
• Publications: 0 publications found

Genes affected

ENSG00000287291 (HGNC:):

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NBAS	XR_007076390.1	n.7016-58115A>T		intron_variant	Intron 53 of 53

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000287291	ENST00000654007.1	n.857-123967A>T		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44585 AN: 151670 Hom.: 7115 Cov.: 33

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.297

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

GnomAD4 genome AF: 0.294 AC: 44613 AN: 151788 Hom.: 7124 Cov.: 33 AF XY: 0.300 AC XY: 22225 AN XY: 74188

African (AFR) AF: 0.174 AC: 7234 AN: 41504

American (AMR) AF: 0.315 AC: 4798 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1014 AN: 3470

East Asian (EAS) AF: 0.397 AC: 2053 AN: 5166

South Asian (SAS) AF: 0.361 AC: 1741 AN: 4818

European-Finnish (FIN) AF: 0.433 AC: 4568 AN: 10554

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.328 AC: 22231 AN: 67726

Other (OTH) AF: 0.301 AC: 633 AN: 2106

Alfa AF: 0.313 Hom.: 979

Bravo AF: 0.280

Asia WGS AF: 0.377 AC: 1310 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.74
PhyloP100		-0.41

Splicing

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

Other links and lift over

dbSNP: rs1518790; hg19: chr2-14977386;