chr19-41878977-T-A

Variant names:

• chr19-41878977-T-A
• rs2074204310
• NM_001783.4:c.80-13T>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_001783.4(CD79A):​c.80-13T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000071 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00096 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CD79A NM_001783.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• 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: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
• autosomal agammaglobulinemia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001783.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD79A	NM_001783.4	MANE Select	c.80-13T>A		intron	N/A	NP_001774.1	P11912-1
	CD79A	NM_021601.4		c.80-13T>A		intron	N/A	NP_067612.1	P11912-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD79A	ENST00000221972.8	TSL:1 MANE Select	c.80-13T>A		intron	N/A	ENSP00000221972.3	P11912-1
	CD79A	ENST00000444740.2	TSL:1	c.80-13T>A		intron	N/A	ENSP00000400605.1	P11912-2
	CD79A	ENST00000597454.2	TSL:3	c.80-13T>A		intron	N/A	ENSP00000468922.2	M0QX61

Frequencies

GnomAD3 genomes AF: 0.00000709 AC: 1 AN: 140956 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

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: 0.0000156

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000961 AC: 483 AN: 502420 Hom.: 0 Cov.: 13 AF XY: 0.000842 AC XY: 231 AN XY: 274208

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

African (AFR) AF: 0.00117 AC: 16 AN: 13628

American (AMR) AF: 0.000212 AC: 8 AN: 37720

Ashkenazi Jewish (ASJ) AF: 0.000761 AC: 11 AN: 14462

East Asian (EAS) AF: 0.00106 AC: 20 AN: 18880

South Asian (SAS) AF: 0.0000871 AC: 6 AN: 68852

European-Finnish (FIN) AF: 0.000101 AC: 3 AN: 29846

Middle Eastern (MID) AF: 0.000610 AC: 2 AN: 3278

European-Non Finnish (NFE) AF: 0.00136 AC: 398 AN: 293124

Other (OTH) AF: 0.000840 AC: 19 AN: 22630

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000709 AC: 1 AN: 141100 Hom.: 0 Cov.: 31 AF XY: 0.0000146 AC XY: 1 AN XY: 68498

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

African (AFR) AF: 0.00 AC: 0 AN: 39452

American (AMR) AF: 0.00 AC: 0 AN: 14440

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3304

East Asian (EAS) AF: 0.00 AC: 0 AN: 3978

South Asian (SAS) AF: 0.00 AC: 0 AN: 3844

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8758

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.0000156 AC: 1 AN: 64184

Other (OTH) AF: 0.00 AC: 0 AN: 2004

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.64
DANN	Benign	0.45
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.83		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.83		Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2074204310; hg19: chr19-42383047;