dbSNP rs2287833: 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
NUCB1	NM_006184.6 link	c.758-255A>T	intron_variant	Intron 7 of 12	ENST00000405315.9	NP_006175.2	Q02818A8K7Q1
NUCB1-AS1	NR_046633.1 link	n.188+233T>A	intron_variant	Intron 1 of 1
NUCB1	XM_017026845.2 link	c.758-255A>T	intron_variant	Intron 7 of 12		XP_016882334.1	Q02818

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUCB1	ENST00000405315.9 link	c.758-255A>T		intron_variant	Intron 7 of 12	1	NM_006184.6	ENSP00000385923.3		Q02818

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over