rs1330

Positions:

• chr11-17294482-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005013.4(NUCB2):​c.1-842C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 151,778 control chromosomes in the GnomAD database, including 7,347 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 0.30 (7347 hom., cov: 31)
• Consequence: NUCB2 NM_005013.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.272

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUCB2	NM_005013.4	c.1-842C>T		intron_variant		ENST00000529010.6	NP_005004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUCB2	ENST00000529010.6	c.1-842C>T		intron_variant		1	NM_005013.4	ENSP00000436455	P3

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45306 AN: 151658 Hom.: 7350 Cov.: 31

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.299 AC: 45342 AN: 151778 Hom.: 7347 Cov.: 31 AF XY: 0.298 AC XY: 22126 AN XY: 74146

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.366

Gnomad4 ASJ AF: 0.317

Gnomad4 EAS AF: 0.358

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.307

Gnomad4 NFE AF: 0.344

Gnomad4 OTH AF: 0.301

Alfa AF: 0.340 Hom.: 18960

Bravo AF: 0.298

Asia WGS AF: 0.351 AC: 1220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs1330; hg19: chr11-17316029;