NM_000626.4:c.312C>T

Variant names:

• chr17-63930192-G-A
• rs116625909
• NM_000626.4:c.312C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_000626.4(CD79B):​c.312C>T​(p.Leu104Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00145 in 1,614,228 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0079 (15 hom., cov: 33)
  • Exomes 𝑓: 0.00078 (17 hom.)
• Consequence: CD79B NM_000626.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.152
• Publications: 0 publications found

Genes affected

CD79B (HGNC:1699): (CD79b 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-beta protein of the B-cell antigen component. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

CD79B Gene-Disease associations (from GenCC):

• agammaglobulinemia 6, autosomal recessive

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
• autosomal agammaglobulinemia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000285947 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 17-63930192-G-A is Benign according to our data. Variant chr17-63930192-G-A is described in ClinVar as Benign. ClinVar VariationId is 471350.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.152 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00788 (1201/152346) while in subpopulation AFR AF = 0.027 (1124/41580). AF 95% confidence interval is 0.0257. There are 15 homozygotes in GnomAd4. There are 571 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 15 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000626.4. 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
	CD79B	NM_000626.4	MANE Select	c.312C>T	p.Leu104Leu	synonymous	Exon 3 of 6	NP_000617.1
	CD79B	NM_001039933.3		c.315C>T	p.Leu105Leu	synonymous	Exon 3 of 6	NP_001035022.1
	CD79B	NM_001329050.2		c.122-304C>T		intron	N/A	NP_001315979.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD79B	ENST00000006750.8	TSL:1 MANE Select	c.312C>T	p.Leu104Leu	synonymous	Exon 3 of 6	ENSP00000006750.4
	CD79B	ENST00000392795.7	TSL:1	c.315C>T	p.Leu105Leu	synonymous	Exon 3 of 6	ENSP00000376544.3
	ENSG00000285947	ENST00000647774.1		c.50-304C>T		intron	N/A	ENSP00000497443.1

Frequencies

GnomAD3 genomes AF: 0.00788 AC: 1200 AN: 152228 Hom.: 15 Cov.: 33

Gnomad AFR AF: 0.0271

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00353

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00813

GnomAD2 exomes AF: 0.00184 AC: 462 AN: 251412 AF XY: 0.00132

Gnomad AFR exome AF: 0.0260

Gnomad AMR exome AF: 0.000781

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000780 AC: 1140 AN: 1461882 Hom.: 17 Cov.: 34 AF XY: 0.000644 AC XY: 468 AN XY: 727240

African (AFR) AF: 0.0280 AC: 938 AN: 33480

American (AMR) AF: 0.00107 AC: 48 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5768

European-Non Finnish (NFE) AF: 0.0000297 AC: 33 AN: 1112012

Other (OTH) AF: 0.00176 AC: 106 AN: 60396

GnomAD4 genome AF: 0.00788 AC: 1201 AN: 152346 Hom.: 15 Cov.: 33 AF XY: 0.00766 AC XY: 571 AN XY: 74496

African (AFR) AF: 0.0270 AC: 1124 AN: 41580

American (AMR) AF: 0.00353 AC: 54 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68028

Other (OTH) AF: 0.00805 AC: 17 AN: 2112

Alfa AF: 0.00416 Hom.: 5

Bravo AF: 0.00886

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000119

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Agammaglobulinemia 6, autosomal recessive (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.6
DANN	Benign	0.46
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs116625909; hg19: chr17-62007552;