chr2-14864624-T-C

Variant names:

• chr2-14864624-T-C
• rs1157907
• ENST00000654007.1:n.856+122040A>G

Variant summary

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

The ENST00000654007.1(ENSG00000287291):​n.856+122040A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,000 control chromosomes in the GnomAD database, including 7,083 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 (7083 hom., cov: 31)
• Consequence: ENSG00000287291 ENST00000654007.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.87
• Publications: 1 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=-1.05).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NBAS	XR_007076390.1	n.7016-85477A>G		intron_variant	Intron 53 of 53

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000287291	ENST00000654007.1	n.856+122040A>G		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44231 AN: 151880 Hom.: 7078 Cov.: 31

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.297

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

GnomAD4 genome AF: 0.291 AC: 44245 AN: 152000 Hom.: 7083 Cov.: 31 AF XY: 0.297 AC XY: 22031 AN XY: 74302

African (AFR) AF: 0.160 AC: 6655 AN: 41490

American (AMR) AF: 0.313 AC: 4778 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1016 AN: 3470

East Asian (EAS) AF: 0.403 AC: 2076 AN: 5156

South Asian (SAS) AF: 0.362 AC: 1746 AN: 4820

European-Finnish (FIN) AF: 0.431 AC: 4542 AN: 10540

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.331 AC: 22455 AN: 67938

Other (OTH) AF: 0.301 AC: 635 AN: 2112

Alfa AF: 0.314 Hom.: 32705

Bravo AF: 0.277

Asia WGS AF: 0.381 AC: 1328 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.063
DANN	Benign	0.24
PhyloP100		-4.9

Splicing

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

Other links and lift over

dbSNP: rs1157907; hg19: chr2-15004748;