rs148797987

Positions:

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001783.4(CD79A):c.419C>A(p.Thr140Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00179 in 1,611,714 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T140I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 4 hom. )

Consequence

CD79A
NM_001783.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:5B:1O:1

Conservation

PhyloP100: 1.52

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011353046).

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD79A	NM_001783.4 linkuse as main transcript	c.419C>A	p.Thr140Asn	missense_variant	3/5	ENST00000221972.8
CD79A	NM_021601.4 linkuse as main transcript	c.305C>A	p.Thr102Asn	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD79A	ENST00000221972.8 linkuse as main transcript	c.419C>A	p.Thr140Asn	missense_variant	3/5	1	NM_001783.4	P1	P11912-1
CD79A	ENST00000444740.2 linkuse as main transcript	c.305C>A	p.Thr102Asn	missense_variant	3/5	1			P11912-2
CD79A	ENST00000597454.2 linkuse as main transcript	c.664C>A	p.Pro222Thr	missense_variant	2/4	3

Frequencies

GnomAD3 genomes

AF:

0.00133

AC:

202

AN:

152052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00268

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00212

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00134

AC:

328

AN:

243868

Hom.:

AF XY:

0.00134

AC XY:

178

AN XY:

132526

show subpopulations

Gnomad AFR exome

AF:

0.000522

Gnomad AMR exome

AF:

0.00191

Gnomad ASJ exome

AF:

0.000810

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000987

Gnomad NFE exome

AF:

0.00212

Gnomad OTH exome

AF:

0.00202

GnomAD4 exome

AF:

0.00184

AC:

2685

AN:

1459544

Hom.:

Cov.:

AF XY:

0.00178

AC XY:

1289

AN XY:

725940

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.00211

Gnomad4 ASJ exome

AF:

0.000652

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000948

Gnomad4 NFE exome

AF:

0.00219

Gnomad4 OTH exome

AF:

0.00201

GnomAD4 genome

AF:

0.00133

AC:

202

AN:

152170

Hom.:

Cov.:

AF XY:

0.00117

AC XY:

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.00268

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00212

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00190

Hom.:

Bravo

AF:

0.00161

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.000909

AC:

ESP6500EA

AF:

0.00244

AC:

ExAC

AF:

0.00109

AC:

132

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:5Benign:1Other:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:3

Uncertain significance, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Uncertain significance, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Uncertain significance, criteria provided, single submitter	clinical testing	GeneDx	Oct 05, 2022	Reported in two patients with common variable immunodeficiency disorder who also harbored an additional missense variant in the CD79A gene; however, the phase was not reported for these variants (van Schouwenburg et al., 2015); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 24728327, 26122175, 33772212) -

Agammaglobulinemia 3, autosomal recessive

Uncertain:2Benign:1

Uncertain significance, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Aug 15, 2023	The CD79A c.419C>A; p.Thr140Asn variant (rs148797987; ClinVar Variation ID: 133835) is reported in the literature in an individual affected with common variable immunodeficiency, although it was not demonstrated to be pathogenic (Van Schouwenburg 2015). This variant is found in the non-Finnish European population with an overall allele frequency of 0.13% (363/275,170 alleles) in the Genome Aggregation Database. The threonine at codon 140 is highly conserved but computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.408). Based on the available information, the clinical significance of this variant is uncertain. References: Van Schouwenburg et al. Application of whole genome and RNA sequencing to investigate the genomic landscape of common variable immunodeficiency disorders. Clin Immunol. 2015 Oct;160(2):301-14. -
Uncertain significance, criteria provided, single submitter	clinical testing	Baylor Genetics	Mar 20, 2019	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

not specified

Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.62

BayesDel_addAF

Uncertain

0.025

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.29

MetaRNN

Benign

0.011

MutationTaster

Benign

0.57

D;N

Sift4G

Pathogenic

0.0

MVP

0.72

ClinPred

0.045

GERP RS

3.9

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over