19-48918471-A-T

Variant names:

• chr19-48918471-A-T
• rs2287833
• NM_006184.6:c.758-255A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006184.6. 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
	NUCB1	NM_006184.6	MANE Select	c.758-255A>T		intron	N/A	NP_006175.2
	NUCB1-AS1	NR_046633.1		n.188+233T>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUCB1	ENST00000405315.9	TSL:1 MANE Select	c.758-255A>T		intron	N/A	ENSP00000385923.3
	NUCB1	ENST00000460125.1	TSL:2	n.96A>T		non_coding_transcript_exon	Exon 1 of 2
	NUCB1	ENST00000706760.1		c.788-255A>T		intron	N/A	ENSP00000516537.1

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

African (AFR) AF: 0.230 AC: 2303 AN: 10006

American (AMR) AF: 0.510 AC: 7009 AN: 13744

Ashkenazi Jewish (ASJ) AF: 0.506 AC: 5101 AN: 10072

East Asian (EAS) AF: 0.345 AC: 7666 AN: 22250

South Asian (SAS) AF: 0.712 AC: 24396 AN: 34254

European-Finnish (FIN) AF: 0.723 AC: 14223 AN: 19678

Middle Eastern (MID) AF: 0.507 AC: 865 AN: 1706

European-Non Finnish (NFE) AF: 0.649 AC: 125137 AN: 192860

Other (OTH) AF: 0.577 AC: 10880 AN: 18862

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

African (AFR) AF: 0.239 AC: 9912 AN: 41472

American (AMR) AF: 0.522 AC: 7952 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1743 AN: 3464

East Asian (EAS) AF: 0.387 AC: 1988 AN: 5140

South Asian (SAS) AF: 0.736 AC: 3546 AN: 4820

European-Finnish (FIN) AF: 0.752 AC: 7961 AN: 10582

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.658 AC: 44721 AN: 67936

Other (OTH) AF: 0.518 AC: 1091 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.91
PhyloP100		-0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2287833; hg19: chr19-49421728;