17-63929252-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000626.4(CD79B):c.664G>C(p.Val222Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V222I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CD79B NM_000626.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.96

Genes affected

CD79B (HGNC:1699): (CD79b molecule) The B lymphocyte antigen receptor is a multimeric complex that includes the antigen-specific component, surface immunoglobulin (Ig). Surface Ig non-covalently associates with two other proteins, Ig-alpha and Ig-beta, which are necessary for expression and function of the B-cell antigen receptor. This gene encodes the Ig-beta protein of the B-cell antigen component. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26238745).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD79B	NM_000626.4	c.664G>C	p.Val222Leu	missense_variant	6/6	ENST00000006750.8
CD79B	NM_001039933.3	c.667G>C	p.Val223Leu	missense_variant	6/6
CD79B	NM_001329050.2	c.355G>C	p.Val119Leu	missense_variant	5/5
CD79B	NM_021602.4	c.352G>C	p.Val118Leu	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD79B	ENST00000006750.8	c.664G>C	p.Val222Leu	missense_variant	6/6	1	NM_000626.4	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250816 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135636

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 14, 2022

The c.664G>C (p.V222L) alteration is located in exon 6 (coding exon 6) of the CD79B gene. This alteration results from a G to C substitution at nucleotide position 664, causing the valine (V) at amino acid position 222 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
Cadd	Pathogenic	27
Dann	Uncertain	0.99
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.21
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.84	T;T;D
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.26	T;T;T
MetaSVM	Uncertain	0.089	D
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.7	N;N;D
REVEL	Uncertain	0.54
Sift	Uncertain	0.010	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0, 0.99	.;D;D
Vest4		0.35
MutPred		0.58		.;Loss of sheet (P = 0.0817);.;
MVP		0.87
MPC		1.5
ClinPred		0.80	D
GERP RS		4.1
Varity_R		0.15
gMVP		0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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

Other links and lift over

dbSNP: rs144588938; hg19: chr17-62006612;