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: Labcorp Genetics (formerly Invitae), G2P, Orphanet
• short stature-optic atrophy-Pelger-Huët anomaly syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Illumina, G2P, Labcorp Genetics (formerly Invitae)

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000416173.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000235127	ENST00000416173.1	TSL:4	n.360-169G>A		intron	N/A
	ENSG00000287291	ENST00000654007.1		n.856+99741G>A		intron	N/A

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 v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6432484;

hg19: chr2-15027047;