rs6432484

Variant names:

• chr2-14886923-C-T
• rs6432484
• ENST00000416173.1:n.360-169G>A

Variant summary

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

The ENST00000416173.1(ENSG00000235127):​n.360-169G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,016 control chromosomes in the GnomAD database, including 5,395 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 0.23 (5395 hom., cov: 32)
• Consequence: ENSG00000235127 ENST00000416173.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.557
• Publications: 2 publications found

Genes affected

ENSG00000235127 (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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NBAS	XR_007076390.1	n.7016-107776G>A		intron_variant	Intron 53 of 53

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000235127	ENST00000416173.1	n.360-169G>A		intron_variant	Intron 2 of 2	4
ENSG00000287291	ENST00000654007.1	n.856+99741G>A		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34219 AN: 151898 Hom.: 5382 Cov.: 32

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.00636

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.153

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.225 AC: 34276 AN: 152016 Hom.: 5395 Cov.: 32 AF XY: 0.224 AC XY: 16647 AN XY: 74300

African (AFR) AF: 0.441 AC: 18257 AN: 41440

American (AMR) AF: 0.147 AC: 2242 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 619 AN: 3472

East Asian (EAS) AF: 0.00638 AC: 33 AN: 5176

South Asian (SAS) AF: 0.155 AC: 748 AN: 4814

European-Finnish (FIN) AF: 0.178 AC: 1882 AN: 10546

Middle Eastern (MID) AF: 0.158 AC: 46 AN: 292

European-Non Finnish (NFE) AF: 0.146 AC: 9917 AN: 67978

Other (OTH) AF: 0.197 AC: 417 AN: 2114

Alfa AF: 0.170 Hom.: 7334

Bravo AF: 0.228

Asia WGS AF: 0.107 AC: 378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.51
DANN	Benign	0.70
PhyloP100		-0.56

Splicing

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

Other links and lift over

dbSNP: rs6432484; hg19: chr2-15027047;