11-17278870-G-T

Variant names:

• chr11-17278870-G-T
• rs214075
• NM_005013.4:c.-156+2042G>T

Variant summary

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

The NM_005013.4(NUCB2):​c.-156+2042G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 151,986 control chromosomes in the GnomAD database, including 17,071 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 0.46 (17071 hom., cov: 32)
• Consequence: NUCB2 NM_005013.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.166
• Publications: 6 publications found

Genes affected

NUCB2 (HGNC:8044): (nucleobindin 2) This gene encodes a protein with a suggested role in calcium level maintenance, eating regulation in the hypothalamus, and release of tumor necrosis factor from vascular endothelial cells. This protein binds calcium and has EF-folding domains. [provided by RefSeq, Oct 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005013.4. 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
	NUCB2	NM_005013.4	MANE Select	c.-156+2042G>T		intron	N/A	NP_005004.1
	NUCB2	NM_001352661.2		c.-363+2042G>T		intron	N/A	NP_001339590.1
	NUCB2	NM_001352663.2		c.-279+2042G>T		intron	N/A	NP_001339592.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUCB2	ENST00000529010.6	TSL:1 MANE Select	c.-156+2042G>T		intron	N/A	ENSP00000436455.1
	NUCB2	ENST00000526120.5	TSL:1	c.-155-3919G>T		intron	N/A	ENSP00000436215.1
	NUCB2	ENST00000533738.6	TSL:1	c.-240+2042G>T		intron	N/A	ENSP00000435558.1

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70558 AN: 151866 Hom.: 17036 Cov.: 32

Gnomad AFR AF: 0.545

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.800

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.459

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

GnomAD4 genome AF: 0.465 AC: 70646 AN: 151986 Hom.: 17071 Cov.: 32 AF XY: 0.465 AC XY: 34539 AN XY: 74280

African (AFR) AF: 0.546 AC: 22613 AN: 41424

American (AMR) AF: 0.410 AC: 6256 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.516 AC: 1791 AN: 3470

East Asian (EAS) AF: 0.800 AC: 4134 AN: 5168

South Asian (SAS) AF: 0.540 AC: 2606 AN: 4830

European-Finnish (FIN) AF: 0.370 AC: 3903 AN: 10558

Middle Eastern (MID) AF: 0.322 AC: 94 AN: 292

European-Non Finnish (NFE) AF: 0.410 AC: 27835 AN: 67956

Other (OTH) AF: 0.460 AC: 970 AN: 2108

Alfa AF: 0.431 Hom.: 3964

Bravo AF: 0.472

Asia WGS AF: 0.623 AC: 2168 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	7.7
DANN	Benign	0.67
PhyloP100		0.17
Mutation Taster		=99/1	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: rs214075; hg19: chr11-17300417;