rs12979328

Positions:

• chr19-48921124-C-A

Variant summary

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

The NM_006184.6(NUCB1):​c.1003-30C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 1,575,636 control chromosomes in the GnomAD database, including 377,775 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 0.53 (26501 hom., cov: 33)
  • Exomes 𝑓: 0.69 (351274 hom.)
• Consequence: NUCB1 NM_006184.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.924

Genes affected

NUCB1 (HGNC:8043): (nucleobindin 1) This gene encodes a member of a small calcium-binding EF-hand protein family. The encoded protein is thought to have a key role in Golgi calcium homeostasis and Ca(2+)-regulated signal transduction events. [provided by RefSeq, Jun 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUCB1	NM_006184.6	c.1003-30C>A		intron_variant		ENST00000405315.9
NUCB1	XM_017026845.2	c.1003-30C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUCB1	ENST00000405315.9	c.1003-30C>A		intron_variant		1	NM_006184.6	P2

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80879 AN: 151966 Hom.: 26510 Cov.: 33

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.700

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.632

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.712

Gnomad FIN AF: 0.770

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.720

Gnomad OTH AF: 0.551

GnomAD3 exomes AF: 0.629 AC: 142795 AN: 227122 Hom.: 48325 AF XY: 0.648 AC XY: 80165 AN XY: 123628

Gnomad AFR exome AF: 0.126

Gnomad AMR exome AF: 0.543

Gnomad ASJ exome AF: 0.648

Gnomad EAS exome AF: 0.396

Gnomad SAS exome AF: 0.708

Gnomad FIN exome AF: 0.760

Gnomad NFE exome AF: 0.721

Gnomad OTH exome AF: 0.653

GnomAD4 exome AF: 0.693 AC: 986689 AN: 1423550 Hom.: 351274 Cov.: 36 AF XY: 0.696 AC XY: 489800 AN XY: 703542

Gnomad4 AFR exome AF: 0.118

Gnomad4 AMR exome AF: 0.551

Gnomad4 ASJ exome AF: 0.650

Gnomad4 EAS exome AF: 0.369

Gnomad4 SAS exome AF: 0.707

Gnomad4 FIN exome AF: 0.758

Gnomad4 NFE exome AF: 0.727

Gnomad4 OTH exome AF: 0.644

GnomAD4 genome AF: 0.532 AC: 80876 AN: 152086 Hom.: 26501 Cov.: 33 AF XY: 0.537 AC XY: 39892 AN XY: 74328

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.553

Gnomad4 ASJ AF: 0.632

Gnomad4 EAS AF: 0.388

Gnomad4 SAS AF: 0.711

Gnomad4 FIN AF: 0.770

Gnomad4 NFE AF: 0.720

Gnomad4 OTH AF: 0.549

Alfa AF: 0.677 Hom.: 31851

Bravo AF: 0.496

Asia WGS AF: 0.562 AC: 1953 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.7
DANN	Benign	0.84
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12979328; hg19: chr19-49424381;