Genetic Variant NUCB1:c.758-255A>T (chr19-48918471-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.813

Publications

3 publications found

Variant links:

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 links:

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

NUCB1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Sel.	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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NUCB1	ENST00000405315.9	TSL:1 MANE Select	c.758-255A>T	intron	N/A	ENSP00000385923.3	Q02818
NUCB1	ENST00000878482.1		c.854-255A>T	intron	N/A	ENSP00000548541.1
NUCB1	ENST00000941802.1		c.854-255A>T	intron	N/A	ENSP00000611861.1

Frequencies

GnomAD3 genomes

AF:

0.524

AC:

79609

AN:

151848

Hom.:

23709

Cov.:

show subpopulations

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.:

AF XY:

0.619

AC XY:

105081

AN XY:

169776

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

3216

6432

9649

12865

16081

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

560

1120

1680

2240

2800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.524

AC:

79639

AN:

151966

Hom.:

23721

Cov.:

AF XY:

0.531

AC XY:

39420

AN XY:

74268

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1686

3372

5057

6743

8429

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

684

1368

2052

2736

3420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

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)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over