11-17267807-A-G

Position:

• chr11-17267807-A-G

Variant summary

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

The ENST00000530527.5(NUCB2):​c.-1002+126A>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 ENST00000530527.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0340

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUCB2	ENST00000528644.5	c.-155-14982A>G		intron_variant		4		ENSP00000431136
NUCB2	ENST00000530527.5	c.-1002+126A>G		intron_variant		2		ENSP00000435160
NUCB2	ENST00000646648.1	c.-498-1378A>G		intron_variant, NMD_transcript_variant				ENSP00000495210
NUCB2	ENST00000620945.1	n.930-261A>G		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.688

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.154

Gnomad4 NFE exome AF: 0.294

Gnomad4 OTH exome AF: 0.300

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

Gnomad4 AFR AF: 0.551

Gnomad4 AMR AF: 0.418

Gnomad4 ASJ AF: 0.516

Gnomad4 EAS AF: 0.798

Gnomad4 SAS AF: 0.537

Gnomad4 FIN AF: 0.365

Gnomad4 NFE AF: 0.413

Gnomad4 OTH AF: 0.463

Alfa AF: 0.436 Hom.: 2435

Bravo AF: 0.477

Asia WGS AF: 0.627 AC: 2180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs214101; hg19: chr11-17289354;