dbSNP rs12979328: NUCB1:c.1003-30C>A (chr19-48921124-C-A) – 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.1003-30C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 1,575,636 control chromosomes in the GnomAD database, including 377,775 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 0.53 ( 26501 hom., cov: 33)

Exomes 𝑓: 0.69 ( 351274 hom. )

Consequence

NUCB1
NM_006184.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.924

Publications

13 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:

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=-0.79).

BA1

GnomAd4 highest subpopulation (NFE) 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.1003-30C>A		intron	N/A	NP_006175.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NUCB1	ENST00000405315.9	TSL:1 MANE Select	c.1003-30C>A	intron	N/A	ENSP00000385923.3	Q02818
NUCB1	ENST00000878482.1		c.1099-30C>A	intron	N/A	ENSP00000548541.1
NUCB1	ENST00000941802.1		c.1099-30C>A	intron	N/A	ENSP00000611861.1

Frequencies

GnomAD3 genomes

AF:

0.532

AC:

80879

AN:

151966

Hom.:

26510

Cov.:

show subpopulations

Gnomad AFR

AF:

0.139

Gnomad AMI

AF:

0.700

Gnomad AMR

AF:

0.552

Gnomad ASJ

AF:

0.632

Gnomad EAS

AF:

0.388

Gnomad SAS

AF:

0.712

Gnomad FIN

AF:

0.770

Gnomad MID

AF:

0.579

Gnomad NFE

AF:

0.720

Gnomad OTH

AF:

0.551

GnomAD2 exomes

AF:

0.629

AC:

142795

AN:

227122

AF XY:

0.648

show subpopulations

Gnomad AFR exome

AF:

0.126

Gnomad AMR exome

AF:

0.543

Gnomad ASJ exome

AF:

0.648

Gnomad EAS exome

AF:

0.396

Gnomad FIN exome

AF:

0.760

Gnomad NFE exome

AF:

0.721

Gnomad OTH exome

AF:

0.653

GnomAD4 exome

AF:

0.693

AC:

986689

AN:

1423550

Hom.:

351274

Cov.:

AF XY:

0.696

AC XY:

489800

AN XY:

703542

show subpopulations

African (AFR)

AF:

0.118

AC:

3814

AN:

32318

American (AMR)

AF:

0.551

AC:

22041

AN:

40026

Ashkenazi Jewish (ASJ)

AF:

0.650

AC:

15703

AN:

24172

East Asian (EAS)

AF:

0.369

AC:

14430

AN:

39082

South Asian (SAS)

AF:

0.707

AC:

58261

AN:

82352

European-Finnish (FIN)

AF:

0.758

AC:

39025

AN:

51514

Middle Eastern (MID)

AF:

0.620

AC:

3424

AN:

5520

European-Non Finnish (NFE)

AF:

0.727

AC:

792300

AN:

1090068

Other (OTH)

AF:

0.644

AC:

37691

AN:

58498

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

15137

30273

45410

60546

75683

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19710

39420

59130

78840

98550

<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:

0.532

AC:

80876

AN:

152086

Hom.:

26501

Cov.:

AF XY:

0.537

AC XY:

39892

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.139

AC:

5751

AN:

41508

American (AMR)

AF:

0.553

AC:

8431

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.632

AC:

2193

AN:

3470

East Asian (EAS)

AF:

0.388

AC:

2001

AN:

5154

South Asian (SAS)

AF:

0.711

AC:

3430

AN:

4826

European-Finnish (FIN)

AF:

0.770

AC:

8139

AN:

10574

Middle Eastern (MID)

AF:

0.554

AC:

163

AN:

294

European-Non Finnish (NFE)

AF:

0.720

AC:

48976

AN:

67996

Other (OTH)

AF:

0.549

AC:

1155

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1459

2918

4377

5836

7295

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

674

1348

2022

2696

3370

<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:

0.685

Hom.:

47046

Bravo

AF:

0.496

Asia WGS

AF:

0.562

AC:

1953

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

8.7

(source)

DANN

Benign

0.84

PhyloP100

0.92

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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