rs214070

chr11-17283770-T-Achr11-17283770-T-G

Variant summary

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

The NM_005013.4(NUCB2):c.-1+827T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,230 control chromosomes in the GnomAD database, including 4,402 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 0.21 (4402 hom., cov: 33)
• Consequence: NUCB2 NM_005013.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.138

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=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUCB2	NM_005013.4	c.-1+827T>A		intron_variant		ENST00000529010.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUCB2	ENST00000529010.6	c.-1+827T>A		intron_variant		1	NM_005013.4	P3

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32647 AN: 152110 Hom.: 4403 Cov.: 33

Gnomad AFR AF: 0.0529

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.214 AC: 32644 AN: 152230 Hom.: 4402 Cov.: 33 AF XY: 0.215 AC XY: 16031 AN XY: 74414

Gnomad4 AFR AF: 0.0528

Gnomad4 AMR AF: 0.195

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.353

Gnomad4 SAS AF: 0.344

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.285

Gnomad4 OTH AF: 0.213

Alfa AF: 0.241 Hom.: 627

Bravo AF: 0.202

Asia WGS AF: 0.304 AC: 1054 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	14
Dann	Benign	0.87

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: rs214070; hg19: chr11-17305317;