rs2287833

Positions:

• chr19-48918471-A-T

Variant summary

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

The NM_006184.6(NUCB1):​c.758-255A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 475,398 control chromosomes in the GnomAD database, including 86,643 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 0.52 (23721 hom., cov: 31)
  • Exomes 𝑓: 0.61 (62922 hom.)
• Consequence: NUCB1 NM_006184.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.813

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]

NUCB1-AS1 (HGNC:40419): (NUCB1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUCB1	NM_006184.6	c.758-255A>T		intron_variant		ENST00000405315.9	NP_006175.2
NUCB1-AS1	NR_046633.1	n.188+233T>A		intron_variant, non_coding_transcript_variant
NUCB1	XM_017026845.2	c.758-255A>T		intron_variant			XP_016882334.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUCB1	ENST00000405315.9	c.758-255A>T		intron_variant		1	NM_006184.6	ENSP00000385923	P2
NUCB1-AS1	ENST00000416432.1	n.188+233T>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79609 AN: 151848 Hom.: 23709 Cov.: 31

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.736

Gnomad FIN AF: 0.752

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.523

GnomAD4 exome AF: 0.611 AC: 197580 AN: 323432 Hom.: 62922 Cov.: 0 AF XY: 0.619 AC XY: 105081 AN XY: 169776

Gnomad4 AFR exome AF: 0.230

Gnomad4 AMR exome AF: 0.510

Gnomad4 ASJ exome AF: 0.506

Gnomad4 EAS exome AF: 0.345

Gnomad4 SAS exome AF: 0.712

Gnomad4 FIN exome AF: 0.723

Gnomad4 NFE exome AF: 0.649

Gnomad4 OTH exome AF: 0.577

GnomAD4 genome AF: 0.524 AC: 79639 AN: 151966 Hom.: 23721 Cov.: 31 AF XY: 0.531 AC XY: 39420 AN XY: 74268

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.522

Gnomad4 ASJ AF: 0.503

Gnomad4 EAS AF: 0.387

Gnomad4 SAS AF: 0.736

Gnomad4 FIN AF: 0.752

Gnomad4 NFE AF: 0.658

Gnomad4 OTH AF: 0.518

Alfa AF: 0.585 Hom.: 3472

Bravo AF: 0.491

Asia WGS AF: 0.574 AC: 1993 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.91
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs2287833; hg19: chr19-49421728;