11-17329656-A-G

Position:

• chr11-17329656-A-G

Variant summary

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

The NM_005013.4(NUCB2):​c.1003-471A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 152,090 control chromosomes in the GnomAD database, including 7,586 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 (7586 hom., cov: 32)
• Consequence: NUCB2 NM_005013.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64

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]

NUCB2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.07).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUCB2	NM_005013.4	c.1003-471A>G		intron_variant		ENST00000529010.6	NP_005004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUCB2	ENST00000529010.6	c.1003-471A>G		intron_variant		1	NM_005013.4	ENSP00000436455.1
NUCB2	ENST00000646648.1	n.*315-471A>G		intron_variant				ENSP00000495210.1

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45530 AN: 151970 Hom.: 7586 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.516

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.306

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.299 AC: 45551 AN: 152090 Hom.: 7586 Cov.: 32 AF XY: 0.303 AC XY: 22541 AN XY: 74326

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.336

Gnomad4 EAS AF: 0.517

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.354

Gnomad4 OTH AF: 0.291

Alfa AF: 0.211 Hom.: 537

Bravo AF: 0.278

Asia WGS AF: 0.359 AC: 1247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.46
DANN	Benign	0.14

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: rs10832763; hg19: chr11-17351203;