2-15524632-C-T

Variant names:

• chr2-15524632-C-T
• rs7581919
• NM_015909.4:c.746+9911G>A

Variant summary

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

The NM_015909.4(NBAS):​c.746+9911G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.966 in 152,238 control chromosomes in the GnomAD database, including 71,104 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 0.97 (71104 hom., cov: 30)
• Consequence: NBAS NM_015909.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.495
• Publications: 9 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.982 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015909.4. 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
	NBAS	NM_015909.4	MANE Select	c.746+9911G>A		intron	N/A	NP_056993.2
	NBAS	NR_052013.3		n.776+9911G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NBAS	ENST00000281513.10	TSL:1 MANE Select	c.746+9911G>A		intron	N/A	ENSP00000281513.5
	NBAS	ENST00000914564.1		c.746+9911G>A		intron	N/A	ENSP00000584623.1
	NBAS	ENST00000914565.1		c.557+9911G>A		intron	N/A	ENSP00000584624.1

Frequencies

GnomAD3 genomes AF: 0.966 AC: 146997 AN: 152120 Hom.: 71046 Cov.: 30

Gnomad AFR AF: 0.990

Gnomad AMI AF: 0.989

Gnomad AMR AF: 0.976

Gnomad ASJ AF: 0.994

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.990

Gnomad FIN AF: 0.978

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.942

Gnomad OTH AF: 0.978

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

GnomAD4 genome AF: 0.966 AC: 147114 AN: 152238 Hom.: 71104 Cov.: 30 AF XY: 0.969 AC XY: 72146 AN XY: 74428

African (AFR) AF: 0.990 AC: 41101 AN: 41532

American (AMR) AF: 0.976 AC: 14918 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.994 AC: 3452 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5178 AN: 5180

South Asian (SAS) AF: 0.990 AC: 4766 AN: 4816

European-Finnish (FIN) AF: 0.978 AC: 10379 AN: 10610

Middle Eastern (MID) AF: 0.990 AC: 291 AN: 294

European-Non Finnish (NFE) AF: 0.942 AC: 64058 AN: 68024

Other (OTH) AF: 0.979 AC: 2069 AN: 2114

Alfa AF: 0.954 Hom.: 221384

Bravo AF: 0.968

Asia WGS AF: 0.995 AC: 3460 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.26
DANN	Benign	0.62
PhyloP100		-0.49
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs7581919; hg19: chr2-15664756;