rs144367487

Positions:

chr19-41879281-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001783.4(CD79A):c.371G>A(p.Arg124His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00184 in 1,612,416 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R124C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00083 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0019 ( 6 hom. )

Consequence

CD79A
NM_001783.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3O:1

Conservation

PhyloP100: 2.48

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.070124954).

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD79A	NM_001783.4 linkuse as main transcript	c.371G>A	p.Arg124His	missense_variant	2/5	ENST00000221972.8
CD79A	NM_021601.4 linkuse as main transcript	c.265+106G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD79A	ENST00000221972.8 linkuse as main transcript	c.371G>A	p.Arg124His	missense_variant	2/5	1	NM_001783.4	P1	P11912-1
CD79A	ENST00000444740.2 linkuse as main transcript	c.265+106G>A		intron_variant		1			P11912-2
CD79A	ENST00000597454.2 linkuse as main transcript	c.371G>A	p.Arg124His	missense_variant	2/4	3

Frequencies

GnomAD3 genomes

AF:

0.000835

AC:

127

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000761

AC:

187

AN:

245628

Hom.:

AF XY:

0.000788

AC XY:

105

AN XY:

133254

show subpopulations

Gnomad AFR exome

AF:

0.000374

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00158

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.00195

AC:

2846

AN:

1460112

Hom.:

Cov.:

AF XY:

0.00189

AC XY:

1376

AN XY:

726250

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.0000578

Gnomad4 NFE exome

AF:

0.00248

Gnomad4 OTH exome

AF:

0.00104

GnomAD4 genome

AF:

0.000834

AC:

127

AN:

152304

Hom.:

Cov.:

AF XY:

0.000806

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00151

Hom.:

Bravo

AF:

0.000816

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00174

AC:

ExAC

AF:

0.000832

AC:

101

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00125

EpiControl

AF:

0.00148

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	GeneDx	Oct 05, 2022	Reported in a patient with spondyloarthritis; however, no second variant was reported (Sogkas et al., 2020); 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: 33046446, 24728327) -
Uncertain significance, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Agammaglobulinemia 3, autosomal recessive

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 25, 2023

This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 124 of the CD79A protein (p.Arg124His). This variant is present in population databases (rs144367487, gnomAD 0.2%), including at least one homozygous and/or hemizygous individual. This missense change has been observed in individual(s) with rheumatic diseases and hypogammaglobulinaemia (PMID: 33046446). ClinVar contains an entry for this variant (Variation ID: 133834). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

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

Benign

0.24

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.52

D;T

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.85

T;T

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.070

T;T

MetaSVM

Uncertain

0.21

MutationAssessor

Uncertain

2.6

M;.

MutationTaster

Benign

0.86

D;D

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-3.1

D;.

REVEL

Uncertain

0.61

Sift

Uncertain

0.0090

D;.

Sift4G

Uncertain

0.033

D;D

Polyphen

1.0

D;.

Vest4

0.43

MVP

0.87

MPC

1.4

ClinPred

0.076

GERP RS

4.0

Varity_R

0.12

gMVP

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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