dbSNP rs1320: VPREB1:p.Asp76Asn (chr22-22245125-G-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_007128.4(VPREB1):c.226G>A(p.Asp76Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.048 in 1,612,980 control chromosomes in the GnomAD database, including 2,244 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.037 ( 173 hom., cov: 32)

Exomes 𝑓: 0.049 ( 2071 hom. )

Consequence

VPREB1
NM_007128.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.28

Publications

21 publications found

Variant links:

Genes affected

VPREB1 (HGNC:12709): (V-set pre-B cell surrogate light chain 1) The protein encoded by this gene belongs to the immunoglobulin superfamily and is expressed selectively at the early stages of B cell development, namely, in proB and early preB cells. This gene encodes the iota polypeptide chain that is associated with the Ig-mu chain to form a molecular complex which is expressed on the surface of pre-B cells. The complex is thought to regulate Ig gene rearrangements in the early steps of B-cell differentiation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

VPREB1 links:

IGL (HGNC:5853):

IGL 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 (MetaRNN=0.0018067658).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
VPREB1	NM_007128.4 link	c.226G>A	p.Asp76Asn	missense_variant	Exon 2 of 2	ENST00000403807.4	NP_009059.1
VPREB1	NM_001303509.2 link	c.223G>A	p.Asp75Asn	missense_variant	Exon 2 of 2		NP_001290438.1
IGL		n.22245125G>A		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPREB1	ENST00000403807.4 link	c.226G>A	p.Asp76Asn	missense_variant	Exon 2 of 2	1	NM_007128.4	ENSP00000385361.3
VPREB1	ENST00000302273.3 link	c.*83G>A		3_prime_UTR_variant	Exon 2 of 2	3		ENSP00000304590.3

Frequencies

GnomAD3 genomes

AF:

0.0373

AC:

5674

AN:

152016

Hom.:

173

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00870

Gnomad AMI

AF:

0.168

Gnomad AMR

AF:

0.0322

Gnomad ASJ

AF:

0.0236

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00890

Gnomad FIN

AF:

0.0635

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.0561

Gnomad OTH

AF:

0.0240

GnomAD2 exomes

AF:

0.0390

AC:

9698

AN:

248732

AF XY:

0.0390

show subpopulations

Gnomad AFR exome

AF:

0.00886

Gnomad AMR exome

AF:

0.0222

Gnomad ASJ exome

AF:

0.0234

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0647

Gnomad NFE exome

AF:

0.0585

Gnomad OTH exome

AF:

0.0402

GnomAD4 exome

AF:

0.0491

AC:

71757

AN:

1460848

Hom.:

2071

Cov.:

AF XY:

0.0482

AC XY:

35037

AN XY:

726580

show subpopulations

African (AFR)

AF:

0.00717

AC:

240

AN:

33456

American (AMR)

AF:

0.0227

AC:

1013

AN:

44656

Ashkenazi Jewish (ASJ)

AF:

0.0239

AC:

622

AN:

26032

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39676

South Asian (SAS)

AF:

0.0129

AC:

1112

AN:

86188

European-Finnish (FIN)

AF:

0.0665

AC:

3549

AN:

53342

Middle Eastern (MID)

AF:

0.0120

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.0564

AC:

62655

AN:

1111392

Other (OTH)

AF:

0.0414

AC:

2496

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

4500

9000

13501

18001

22501

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2224

4448

6672

8896

11120

<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:

0.0373

AC:

5674

AN:

152132

Hom.:

173

Cov.:

AF XY:

0.0360

AC XY:

2679

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.00867

AC:

360

AN:

41504

American (AMR)

AF:

0.0323

AC:

493

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0236

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5140

South Asian (SAS)

AF:

0.00891

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0635

AC:

674

AN:

10608

Middle Eastern (MID)

AF:

0.0103

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0561

AC:

3816

AN:

67990

Other (OTH)

AF:

0.0237

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

268

536

803

1071

1339

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

192

256

320

<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:

0.0474

Hom.:

370

Bravo

AF:

0.0345

TwinsUK

AF:

0.0526

AC:

195

ALSPAC

AF:

0.0493

AC:

190

ESP6500AA

AF:

0.00908

AC:

ESP6500EA

AF:

0.0543

AC:

467

ExAC

AF:

0.0406

AC:

4934

Asia WGS

AF:

0.00433

AC:

AN:

3476

EpiCase

AF:

0.0501

EpiControl

AF:

0.0501

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.71

CADD

Benign

9.2

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.31

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0046

LIST_S2

Benign

0.38

T;T

MetaRNN

Benign

0.0018

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.49

N;.

PhyloP100

-3.3

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.061

Sift

Benign

0.32

T;T

Sift4G

Benign

0.27

T;T

Polyphen

0.019

B;.

Vest4

0.018

MPC

0.059

ClinPred

0.0046

GERP RS

-3.7

PromoterAI

0.0028

Neutral

(source)

Varity_R

0.24

gMVP

0.34

Mutation Taster

=93/7

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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