2-14812061-T-C

Variant names:

• chr2-14812061-T-C
• rs6724694
• ENST00000654007.1:n.857-98766A>G

Variant summary

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

The ENST00000654007.1(ENSG00000287291):​n.857-98766A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 152,010 control chromosomes in the GnomAD database, including 13,265 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 0.41 (13265 hom., cov: 32)
• Consequence: ENSG00000287291 ENST00000654007.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.678
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NBAS	XR_007076390.1	n.7016-32914A>G		intron_variant	Intron 53 of 53

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000287291	ENST00000654007.1	n.857-98766A>G		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61822 AN: 151892 Hom.: 13245 Cov.: 32

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.376

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

GnomAD4 genome AF: 0.407 AC: 61893 AN: 152010 Hom.: 13265 Cov.: 32 AF XY: 0.409 AC XY: 30415 AN XY: 74282

African (AFR) AF: 0.538 AC: 22303 AN: 41438

American (AMR) AF: 0.361 AC: 5518 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1147 AN: 3468

East Asian (EAS) AF: 0.385 AC: 1988 AN: 5160

South Asian (SAS) AF: 0.398 AC: 1916 AN: 4820

European-Finnish (FIN) AF: 0.459 AC: 4843 AN: 10560

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.338 AC: 23002 AN: 67972

Other (OTH) AF: 0.380 AC: 801 AN: 2110

Alfa AF: 0.354 Hom.: 37358

Bravo AF: 0.406

Asia WGS AF: 0.413 AC: 1441 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.46
DANN	Benign	0.80
PhyloP100		-0.68

Splicing

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

Other links and lift over

dbSNP: rs6724694; hg19: chr2-14952185;