rs1555843439

Variant names:

• chr19-41878978-G-A
• rs1555843439
• NM_001783.4:c.80-12G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-41878978-G-A
• chr19-41878978-G-C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_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

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

ACMG classification

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	c.80-12G>A		intron_variant	Intron 1 of 4	ENST00000221972.8	NP_001774.1
CD79A	NM_021601.4	c.80-12G>A		intron_variant	Intron 1 of 4		NP_067612.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00000669 AC: 1 AN: 149378 Hom.: 0 Cov.: 31

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: 1 AN: 1114540 Hom.: 0 Cov.: 26 AF XY: 0.00000178 AC XY: 1 AN XY: 560788

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

African (AFR) AF: 0.00 AC: 0 AN: 25478

American (AMR) AF: 0.00 AC: 0 AN: 40078

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19724

East Asian (EAS) AF: 0.00 AC: 0 AN: 28622

South Asian (SAS) AF: 0.00 AC: 0 AN: 80772

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4568

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 837438

Other (OTH) AF: 0.00 AC: 0 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.

GnomAD4 genome AF: 0.00000669 AC: 1 AN: 149514 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 73016

African (AFR) AF: 0.0000244 AC: 1 AN: 40922

American (AMR) AF: 0.00 AC: 0 AN: 15066

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3444

East Asian (EAS) AF: 0.00 AC: 0 AN: 4842

South Asian (SAS) AF: 0.00 AC: 0 AN: 4548

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9990

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67440

Other (OTH) AF: 0.00 AC: 0 AN: 2074

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.0090
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

Other links and lift over

dbSNP: rs1555843439; hg19: chr19-42383048;