19-48920990-C-T

Position:

• chr19-48920990-C-T

Variant summary

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

The NM_006184.6(NUCB1):​c.1003-164C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.816 in 152,142 control chromosomes in the GnomAD database, including 54,576 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 0.82 (54576 hom., cov: 31)
• Consequence: NUCB1 NM_006184.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.142

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUCB1	NM_006184.6	c.1003-164C>T		intron_variant		ENST00000405315.9	NP_006175.2
NUCB1	XM_017026845.2	c.1003-164C>T		intron_variant			XP_016882334.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUCB1	ENST00000405315.9	c.1003-164C>T		intron_variant		1	NM_006184.6	ENSP00000385923.3

Frequencies

GnomAD3 genomes AF: 0.817 AC: 124166 AN: 152024 Hom.: 54576 Cov.: 31

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.998

Gnomad AMR AF: 0.890

Gnomad ASJ AF: 0.915

Gnomad EAS AF: 0.964

Gnomad SAS AF: 0.953

Gnomad FIN AF: 0.982

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.965

Gnomad OTH AF: 0.847

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.816 AC: 124194 AN: 152142 Hom.: 54576 Cov.: 31 AF XY: 0.821 AC XY: 61075 AN XY: 74370

Gnomad4 AFR AF: 0.455

Gnomad4 AMR AF: 0.891

Gnomad4 ASJ AF: 0.915

Gnomad4 EAS AF: 0.963

Gnomad4 SAS AF: 0.952

Gnomad4 FIN AF: 0.982

Gnomad4 NFE AF: 0.965

Gnomad4 OTH AF: 0.843

Alfa AF: 0.896 Hom.: 12654

Bravo AF: 0.793

Asia WGS AF: 0.906 AC: 3147 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs9676447; hg19: chr19-49424247;