rs121912424

chr17-63930095-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3_Moderate PP5

The NM_000626.4(CD79B):c.409G>A(p.Gly137Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CD79B NM_000626.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 1.39

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 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.916
• PP5: Variant 17-63930095-C-T is Pathogenic according to our data. Variant chr17-63930095-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 14802.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD79B	NM_000626.4	c.409G>A	p.Gly137Ser	missense_variant	3/6	ENST00000006750.8
CD79B	NM_001039933.3	c.412G>A	p.Gly138Ser	missense_variant	3/6
CD79B	NM_001329050.2	c.122-207G>A		intron_variant
CD79B	NM_021602.4	c.119-207G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD79B	ENST00000006750.8	c.409G>A	p.Gly137Ser	missense_variant	3/6	1	NM_000626.4	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461712 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727132

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Agammaglobulinemia 6, autosomal recessive Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Aug 15, 2007

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
Cadd	Uncertain	24
Dann	Uncertain	1.0
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.72	T;T
M_CAP	Pathogenic	0.67	D
MetaRNN	Pathogenic	0.92	D;D
MetaSVM	Pathogenic	0.97	D
MutationTaster	Benign	1.0	A;A;A
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-5.3	D;D
REVEL	Pathogenic	0.84
Sift	Benign	0.066	T;T
Sift4G	Benign	0.073	T;T
Polyphen		1.0	.;D
Vest4		0.80
MutPred		0.95		.;Loss of sheet (P = 0.0817);
MVP		0.90
MPC		1.2
ClinPred		0.99	D
GERP RS		4.7
Varity_R		0.68
gMVP		0.89

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs121912424; hg19: chr17-62007455; COSMIC: COSV50077075; COSMIC: COSV50077075;