Variant rs757081 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005013.4(NUCB2):c.1012C>G(p.Gln338Glu) variant causes a missense change. The variant allele was found at a frequency of 0.296 in 1,455,928 control chromosomes in the GnomAD database, including 66,585 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.25 ( 5878 hom., cov: 32)

Exomes 𝑓: 0.30 ( 60707 hom. )

Consequence

NUCB2
NM_005013.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.26

Variant links:

Genes affected

NUCB2 (HGNC:8044): (nucleobindin 2) This gene encodes a protein with a suggested role in calcium level maintenance, eating regulation in the hypothalamus, and release of tumor necrosis factor from vascular endothelial cells. This protein binds calcium and has EF-folding domains. [provided by RefSeq, Oct 2011]

NUCB2 links:

NUCB2 (HGNC:):

NUCB2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002201289).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUCB2	NM_005013.4 linkuse as main transcript	c.1012C>G	p.Gln338Glu	missense_variant	12/14	ENST00000529010.6	NP_005004.1	P80303-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NUCB2	ENST00000529010.6 linkuse as main transcript	c.1012C>G	p.Gln338Glu	missense_variant	12/14	1	NM_005013.4	ENSP00000436455.1	P80303-1
NUCB2	ENST00000646648.1 linkuse as main transcript	n.*324C>G		non_coding_transcript_exon_variant	14/17			ENSP00000495210.1	A0A2R8Y6G7
NUCB2	ENST00000646648.1 linkuse as main transcript	n.*324C>G		3_prime_UTR_variant	14/17			ENSP00000495210.1	A0A2R8Y6G7

Frequencies

GnomAD3 genomes

AF:

0.251

AC:

38125

AN:

151670

Hom.:

5881

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0616

Gnomad AMI

AF:

0.479

Gnomad AMR

AF:

0.292

Gnomad ASJ

AF:

0.310

Gnomad EAS

AF:

0.352

Gnomad SAS

AF:

0.319

Gnomad FIN

AF:

0.313

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.329

Gnomad OTH

AF:

0.268

GnomAD3 exomes

AF:

0.302

AC:

61519

AN:

203674

Hom.:

9753

AF XY:

0.304

AC XY:

33755

AN XY:

110932

show subpopulations

Gnomad AFR exome

AF:

0.0516

Gnomad AMR exome

AF:

0.338

Gnomad ASJ exome

AF:

0.302

Gnomad EAS exome

AF:

0.346

Gnomad SAS exome

AF:

0.304

Gnomad FIN exome

AF:

0.317

Gnomad NFE exome

AF:

0.319

Gnomad OTH exome

AF:

0.300

GnomAD4 exome

AF:

0.301

AC:

393040

AN:

1304140

Hom.:

60707

Cov.:

AF XY:

0.303

AC XY:

197153

AN XY:

650092

show subpopulations

Gnomad4 AFR exome

AF:

0.0437

Gnomad4 AMR exome

AF:

0.335

Gnomad4 ASJ exome

AF:

0.303

Gnomad4 EAS exome

AF:

0.328

Gnomad4 SAS exome

AF:

0.304

Gnomad4 FIN exome

AF:

0.328

Gnomad4 NFE exome

AF:

0.307

Gnomad4 OTH exome

AF:

0.285

GnomAD4 genome

AF:

0.251

AC:

38131

AN:

151788

Hom.:

5878

Cov.:

AF XY:

0.251

AC XY:

18649

AN XY:

74182

show subpopulations

Gnomad4 AFR

AF:

0.0615

Gnomad4 AMR

AF:

0.292

Gnomad4 ASJ

AF:

0.310

Gnomad4 EAS

AF:

0.351

Gnomad4 SAS

AF:

0.320

Gnomad4 FIN

AF:

0.313

Gnomad4 NFE

AF:

0.329

Gnomad4 OTH

AF:

0.270

Alfa

AF:

0.317

Hom.:

6020

Bravo

AF:

0.245

TwinsUK

AF:

0.323

AC:

1196

ALSPAC

AF:

0.336

AC:

1296

ESP6500AA

AF:

0.0583

AC:

210

ESP6500EA

AF:

0.320

AC:

2604

ExAC

AF:

0.290

AC:

34912

Asia WGS

AF:

0.300

AC:

1043

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.041

.;T;T;T

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.91

D;.;D;T

MetaRNN

Benign

0.0022

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.5

L;L;L;.

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.080

N;N;.;N

REVEL

Benign

0.072

Sift

Benign

0.37

T;T;.;T

Sift4G

Benign

0.69

T;T;T;T

Polyphen

0.054

.;B;B;.

Vest4

0.13

MPC

0.12

ClinPred

0.0095

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.16

gMVP

0.32

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over