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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUCB1	NM_006184.6 link	c.1003-30C>A		intron_variant	Intron 10 of 12	ENST00000405315.9	NP_006175.2	Q02818A8K7Q1
NUCB1	XM_017026845.2 link	c.1003-30C>A		intron_variant	Intron 10 of 12		XP_016882334.1	Q02818

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUCB1	ENST00000405315.9 link	c.1003-30C>A		intron_variant	Intron 10 of 12	1	NM_006184.6	ENSP00000385923.3		Q02818

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

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

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 v4.3

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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rs12979328

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