Genetic Variant ENST00000647774.1:c.287-2127A>T (chr17-63931377-C-A) – 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 ENST00000647774.1(ENSG00000285947):c.7G>T(p.Val3Leu) 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 1,461,722 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ENSG00000285947
ENST00000647774.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.606

Publications

0 publications found

Variant links:

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: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
autosomal agammaglobulinemia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CD79B links:

ENSG00000285947 (HGNC:):

ENSG00000285947 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=0.12055525).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CD79B	NM_000626.4	MANE Select	c.76G>T	p.Val26Leu	missense	Exon 2 of 6	NP_000617.1	P40259-1
CD79B	NM_001039933.3		c.79G>T	p.Val27Leu	missense	Exon 2 of 6	NP_001035022.1	P40259-3
CD79B	NM_001329050.2		c.79G>T	p.Val27Leu	missense	Exon 2 of 5	NP_001315979.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CD79B	ENST00000006750.8	TSL:1 MANE Select	c.76G>T	p.Val26Leu	missense	Exon 2 of 6	ENSP00000006750.4	P40259-1
ENSG00000285947	ENST00000647774.1		c.7G>T	p.Val3Leu	missense	Exon 1 of 8	ENSP00000497443.1	A0A3B3ISS9
CD79B	ENST00000392795.7	TSL:1	c.79G>T	p.Val27Leu	missense	Exon 2 of 6	ENSP00000376544.3	P40259-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461722

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727172

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53296

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111978

Other (OTH)

AF:

0.00

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.0014

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.35

Eigen

Benign

-0.96

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.53

M_CAP

Benign

0.036

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.7

PhyloP100

0.61

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.61

REVEL

Benign

0.15

Sift

Benign

0.18

Sift4G

Benign

0.18

Polyphen

0.24

Vest4

0.36

MutPred

0.21

Loss of sheet (P = 0.0037)

MVP

0.77

MPC

0.83

ClinPred

0.056

GERP RS

1.1

PromoterAI

0.091

Neutral

(source)

Varity_R

0.096

gMVP

0.60

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over