XM_017004317.2:c.*49-55471C>G

Variant names:

• chr2-15053695-G-C
• rs10206283
• XM_017004317.2:c.*49-55471C>G

Variant summary

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

The XM_017004317.2(NBAS):​c.*49-55471C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 151,630 control chromosomes in the GnomAD database, including 6,705 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 (6705 hom., cov: 31)
• Consequence: NBAS XM_017004317.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.837
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NBAS	XM_017004317.2	c.*49-55471C>G		intron_variant	Intron 52 of 52		XP_016859806.1
NBAS	XR_007076390.1	n.7015+30170C>G		intron_variant	Intron 53 of 53

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43319 AN: 151512 Hom.: 6702 Cov.: 31

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.0978

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.286 AC: 43344 AN: 151630 Hom.: 6705 Cov.: 31 AF XY: 0.283 AC XY: 20953 AN XY: 74084

African (AFR) AF: 0.404 AC: 16713 AN: 41322

American (AMR) AF: 0.216 AC: 3289 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1030 AN: 3460

East Asian (EAS) AF: 0.0982 AC: 506 AN: 5152

South Asian (SAS) AF: 0.251 AC: 1198 AN: 4774

European-Finnish (FIN) AF: 0.263 AC: 2769 AN: 10534

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.250 AC: 16943 AN: 67856

Other (OTH) AF: 0.276 AC: 579 AN: 2098

Alfa AF: 0.147 Hom.: 269

Bravo AF: 0.286

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.20
DANN	Benign	0.50
PhyloP100		-0.84

Splicing

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

Other links and lift over

dbSNP: rs10206283; hg19: chr2-15193819;