ENST00000647774.1:c.287-633G>T

Variant names:

• chr17-63929883-T-A
• NM_000626.4:c.436A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000647774.1(ENSG00000285947):​c.55A>T​(p.Ser19Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ENSG00000285947 ENST00000647774.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.19
• Publications: 1 publications found

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]

CD79B Gene-Disease associations (from GenCC):

• agammaglobulinemia 6, autosomal recessive

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• autosomal agammaglobulinemia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000285947 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000647774.1. 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
	CD79B	NM_000626.4	MANE Select	c.436A>T	p.Ser146Cys	missense	Exon 4 of 6	NP_000617.1	P40259-1
	CD79B	NM_001039933.3		c.439A>T	p.Ser147Cys	missense	Exon 4 of 6	NP_001035022.1	P40259-3
	CD79B	NM_001329050.2		c.127A>T	p.Ser43Cys	missense	Exon 3 of 5	NP_001315979.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD79B	ENST00000006750.8	TSL:1 MANE Select	c.436A>T	p.Ser146Cys	missense	Exon 4 of 6	ENSP00000006750.4	P40259-1
	ENSG00000285947	ENST00000647774.1		c.55A>T	p.Ser19Cys	missense	Exon 2 of 8	ENSP00000497443.1	A0A3B3ISS9
	CD79B	ENST00000392795.7	TSL:1	c.439A>T	p.Ser147Cys	missense	Exon 4 of 6	ENSP00000376544.3	P40259-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Uncertain	0.050	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.90	D
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.65	T
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Uncertain	0.0012	D
MutationAssessor	Benign	0.97	L
PhyloP100		4.2
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.64
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.43
MutPred		0.60		Loss of disorder (P = 0.0571)
MVP		0.70
MPC		1.5
ClinPred		0.94	D
GERP RS		5.6
Varity_R		0.31
gMVP		0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr17-62007243;