Genetic Variant CD79A:c.80-12G>A (chr19-41878978-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001783.4(CD79A):c.80-12G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000158 in 1,264,054 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 31)

Exomes 𝑓: 9.0e-7 ( 0 hom. )

Consequence

CD79A
NM_001783.4 intron

Scores

Splicing: ADA: 0.00002051

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.81

Publications

0 publications found

Variant links:

Genes affected

CD79A (HGNC:1698): (CD79a 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-alpha protein of the B-cell antigen component. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

CD79A Gene-Disease associations (from GenCC):

agammaglobulinemia 3, autosomal recessive
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
autosomal agammaglobulinemia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CD79A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 19-41878978-G-A is Benign according to our data. Variant chr19-41878978-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1950396.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD79A	NM_001783.4 link	c.80-12G>A		intron_variant	Intron 1 of 4	ENST00000221972.8	NP_001774.1	P11912-1
CD79A	NM_021601.4 link	c.80-12G>A		intron_variant	Intron 1 of 4		NP_067612.1	P11912-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CD79A	ENST00000221972.8 link	c.80-12G>A	intron_variant	Intron 1 of 4	1	NM_001783.4	ENSP00000221972.3	P11912-1
CD79A	ENST00000444740.2 link	c.80-12G>A	intron_variant	Intron 1 of 4	1		ENSP00000400605.1	P11912-2
CD79A	ENST00000597454.2 link	c.80-12G>A	intron_variant	Intron 1 of 3	3		ENSP00000468922.2	M0QX61

Frequencies

GnomAD3 genomes

AF:

0.00000669

AC:

AN:

149378

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000245

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

8.97e-7

AC:

AN:

1114540

Hom.:

Cov.:

AF XY:

0.00000178

AC XY:

AN XY:

560788

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

25478

American (AMR)

AF:

0.00

AC:

AN:

40078

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19724

East Asian (EAS)

AF:

0.00

AC:

AN:

28622

South Asian (SAS)

AF:

0.00

AC:

AN:

80772

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4568

European-Non Finnish (NFE)

AF:

0.00000119

AC:

AN:

837438

Other (OTH)

AF:

0.00

AC:

AN:

44240

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000669

AC:

AN:

149514

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73016

show subpopulations

African (AFR)

AF:

0.0000244

AC:

AN:

40922

American (AMR)

AF:

0.00

AC:

AN:

15066

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3444

East Asian (EAS)

AF:

0.00

AC:

AN:

4842

South Asian (SAS)

AF:

0.00

AC:

AN:

4548

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9990

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67440

Other (OTH)

AF:

0.00

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.725

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Agammaglobulinemia 3, autosomal recessive

Benign:1

Aug 28, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.0090

(source)

DANN

Benign

0.44

PhyloP100

-3.8

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000021

dbscSNV1_RF

Benign

0.0060

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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chr19-41878978-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over