rs200057782

Variant names:

• chr22-22245173-G-A
• rs200057782
• NM_007128.4:c.274G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_007128.4(VPREB1):​c.274G>A​(p.Asp92Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000161 in 1,597,968 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: VPREB1 NM_007128.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.10
• Publications: 0 publications found

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]

IGL (HGNC:5853):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.19503546).

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.274G>A	p.Asp92Asn	missense	Exon 2 of 2	NP_009059.1	P12018
	VPREB1	NM_001303509.2		c.271G>A	p.Asp91Asn	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.274G>A	p.Asp92Asn	missense	Exon 2 of 2	ENSP00000385361.3	P12018
	VPREB1	ENST00000302273.3	TSL:3	c.*131G>A		3_prime_UTR	Exon 2 of 2	ENSP00000304590.3	F8W8C9

Frequencies

GnomAD3 genomes AF: 0.0000855 AC: 13 AN: 152116 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000119 AC: 28 AN: 235310 AF XY: 0.000127

Gnomad AFR exome AF: 0.0000625

Gnomad AMR exome AF: 0.0000606

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000486

Gnomad NFE exome AF: 0.000225

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000169 AC: 244 AN: 1445852 Hom.: 0 Cov.: 33 AF XY: 0.000149 AC XY: 107 AN XY: 717606

African (AFR) AF: 0.0000302 AC: 1 AN: 33118

American (AMR) AF: 0.0000461 AC: 2 AN: 43386

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24638

East Asian (EAS) AF: 0.00 AC: 0 AN: 39600

South Asian (SAS) AF: 0.00 AC: 0 AN: 83160

European-Finnish (FIN) AF: 0.0000190 AC: 1 AN: 52716

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5674

European-Non Finnish (NFE) AF: 0.000211 AC: 233 AN: 1103938

Other (OTH) AF: 0.000117 AC: 7 AN: 59622

GnomAD4 genome AF: 0.0000855 AC: 13 AN: 152116 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74304

African (AFR) AF: 0.00 AC: 0 AN: 41434

American (AMR) AF: 0.00 AC: 0 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000121 Hom.: 0

Bravo AF: 0.0000718

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000989 AC: 12

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.60	D
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.54	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.1
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Benign	0.26
Sift	Uncertain	0.026	D
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.19
MVP		0.42
MPC		0.22
ClinPred		0.69	D
GERP RS		3.4
PromoterAI		0.0078	Neutral
Varity_R		0.77
gMVP		0.54
Mutation Taster		=67/33	polymorphism

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

Other links and lift over

dbSNP: rs200057782; hg19: chr22-22599585;