rs148797987

Variant names:

• chr19-41879574-C-A
• rs148797987
• NM_001783.4:c.419C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-41879574-C-A
• chr19-41879574-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

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).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (4 hom.)
• Consequence: CD79A NM_001783.4 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:5 B:1 O:1
• Conservation: PhyloP100: 1.52

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]

ACMG classification

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 rank	MANE	Protein	UniProt
CD79A	NM_001783.4	c.419C>A	p.Thr140Asn	missense_variant	Exon 3 of 5	ENST00000221972.8	NP_001774.1
CD79A	NM_021601.4	c.305C>A	p.Thr102Asn	missense_variant	Exon 3 of 5		NP_067612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD79A	ENST00000221972.8	c.419C>A	p.Thr140Asn	missense_variant	Exon 3 of 5	1	NM_001783.4	ENSP00000221972.3
CD79A	ENST00000444740.2	c.305C>A	p.Thr102Asn	missense_variant	Exon 3 of 5	1		ENSP00000400605.1
CD79A	ENST00000597454.2	c.664C>A	p.Pro222Thr	missense_variant	Exon 2 of 4	3		ENSP00000468922.2

Frequencies

GnomAD3 genomes AF: 0.00133 AC: 202 AN: 152052 Hom.: 0 Cov.: 32

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.: 0 AF XY: 0.00134 AC XY: 178 AN XY: 132526

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.: 4 Cov.: 32 AF XY: 0.00178 AC XY: 1289 AN XY: 725940

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.: 0 Cov.: 32 AF XY: 0.00117 AC XY: 87 AN XY: 74396

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.: 1

Bravo AF: 0.00161

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.00259 AC: 10

ESP6500AA AF: 0.000909 AC: 4

ESP6500EA AF: 0.00244 AC: 21

ExAC AF: 0.00109 AC: 132

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Conflicting classifications of pathogenicity

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

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Uncertain:3

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Oct 05, 2022

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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:2 Benign:1

Mar 20, 2019

Baylor Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -

Aug 15, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Other:1

Sep 19, 2013

ITMI

Significance: not provided

Review Status: no classification provided

Collection Method: reference population

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Uncertain	0.025	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.29	T
MetaRNN	Benign	0.011	T
Sift4G	Pathogenic	0.0	D
MVP		0.72
ClinPred		0.045	T
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

Other links and lift over

dbSNP: rs148797987; hg19: chr19-42383644; COSMIC: COSV55738045; COSMIC: COSV55738045;