11-17267807-A-G

Variant names:

• chr11-17267807-A-G
• rs214101
• ENST00000646648.1:n.-498-1378A>G

Variant summary

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

The ENST00000646648.1(NUCB2):​n.-498-1378A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 151,884 control chromosomes in the GnomAD database, including 17,312 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 0.47 (17296 hom., cov: 30)
  • Exomes 𝑓: 0.33 (16 hom.)
• Consequence: NUCB2 ENST00000646648.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0340
• Publications: 11 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000646648.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUCB2	ENST00000646648.1		n.-498-1378A>G		intron	N/A	ENSP00000495210.1
	NUCB2	ENST00000530527.5	TSL:2	c.-1002+126A>G		intron	N/A	ENSP00000435160.1
	NUCB2	ENST00000528644.5	TSL:4	c.-155-14982A>G		intron	N/A	ENSP00000431136.1

Frequencies

GnomAD3 genomes AF: 0.468 AC: 70966 AN: 151572 Hom.: 17263 Cov.: 30

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.494

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.798

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.462

GnomAD4 exome AF: 0.330 AC: 64 AN: 194 Hom.: 16 AF XY: 0.342 AC XY: 41 AN XY: 120

African (AFR) AF: 0.250 AC: 1 AN: 4

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 4 AN: 4

East Asian (EAS) AF: 0.688 AC: 11 AN: 16

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.154 AC: 4 AN: 26

Middle Eastern (MID) AF: 0.500 AC: 2 AN: 4

European-Non Finnish (NFE) AF: 0.294 AC: 37 AN: 126

Other (OTH) AF: 0.300 AC: 3 AN: 10

GnomAD4 genome AF: 0.468 AC: 71053 AN: 151690 Hom.: 17296 Cov.: 30 AF XY: 0.468 AC XY: 34701 AN XY: 74124

African (AFR) AF: 0.551 AC: 22782 AN: 41324

American (AMR) AF: 0.418 AC: 6360 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.516 AC: 1792 AN: 3472

East Asian (EAS) AF: 0.798 AC: 4107 AN: 5146

South Asian (SAS) AF: 0.537 AC: 2584 AN: 4808

European-Finnish (FIN) AF: 0.365 AC: 3831 AN: 10490

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

European-Non Finnish (NFE) AF: 0.413 AC: 28077 AN: 67916

Other (OTH) AF: 0.463 AC: 977 AN: 2112

Alfa AF: 0.475 Hom.: 4550

Bravo AF: 0.477

Asia WGS AF: 0.627 AC: 2180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	11
DANN	Benign	0.82
PhyloP100		-0.034

Splicing

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

Other links and lift over

dbSNP: rs214101; hg19: chr11-17289354;