Genetic Variant NM_007128.4:c.388G>C (chr22-22245287-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007128.4(VPREB1):c.388G>C(p.Glu130Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

VPREB1
NM_007128.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.36

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.074860126).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007128.4. 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
	VPREB1	NM_007128.4	MANE Select	c.388G>C	p.Glu130Gln	missense	Exon 2 of 2	NP_009059.1	P12018
	VPREB1	NM_001303509.2		c.385G>C	p.Glu129Gln	missense	Exon 2 of 2	NP_001290438.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPREB1	ENST00000403807.4	TSL:1 MANE Select	c.388G>C	p.Glu130Gln	missense	Exon 2 of 2	ENSP00000385361.3	P12018
	VPREB1	ENST00000302273.3	TSL:3	c.*245G>C		3_prime_UTR	Exon 2 of 2	ENSP00000304590.3	F8W8C9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000577

AC:

AN:

173334

AF XY:

0.0000108

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000432

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.15e-7

AC:

AN:

1399064

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

691808

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31392

American (AMR)

AF:

0.0000296

AC:

AN:

33754

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21728

East Asian (EAS)

AF:

0.00

AC:

AN:

39132

South Asian (SAS)

AF:

0.00

AC:

AN:

74874

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5470

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1087214

Other (OTH)

AF:

0.00

AC:

AN:

57872

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.55

CADD

Benign

5.3

(source)

DANN

Benign

0.73

DEOGEN2

Benign

0.12

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.072

LIST_S2

Benign

0.40

M_CAP

Benign

0.013

MetaRNN

Benign

0.075

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

PhyloP100

1.4

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.21

REVEL

Benign

0.013

Sift

Benign

0.20

Sift4G

Benign

0.55

Polyphen

0.22

Vest4

0.24

MutPred

0.39

Loss of sheet (P = 0.1398)

MVP

0.37

MPC

0.052

ClinPred

0.081

GERP RS

0.89

Varity_R

0.31

gMVP

0.27

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over