9-36894154-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016734.3(PAX5):c.911-12049G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0594 in 152,214 control chromosomes in the GnomAD database, including 316 homozygotes. 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 0.059 (316 hom., cov: 32)
• Consequence: PAX5 NM_016734.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.474

Genes affected

PAX5 (HGNC:8619): (paired box 5) This gene encodes a member of the paired box (PAX) family of transcription factors. The central feature of this gene family is a novel, highly conserved DNA-binding motif, known as the paired box. Paired box transcription factors are important regulators in early development, and alterations in the expression of their genes are thought to contribute to neoplastic transformation. This gene encodes the B-cell lineage specific activator protein that is expressed at early, but not late stages of B-cell differentiation. Its expression has also been detected in developing CNS and testis and so the encoded protein may also play a role in neural development and spermatogenesis. This gene is located at 9p13, which is involved in t(9;14)(p13;q32) translocations recurring in small lymphocytic lymphomas of the plasmacytoid subtype, and in derived large-cell lymphomas. This translocation brings the potent E-mu enhancer of the IgH gene into close proximity of the PAX5 promoter, suggesting that the deregulation of transcription of this gene contributes to the pathogenesis of these lymphomas. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.09 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAX5	NM_016734.3	c.911-12049G>A		intron_variant		ENST00000358127.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAX5	ENST00000358127.9	c.911-12049G>A		intron_variant		1	NM_016734.3	P1

Frequencies

GnomAD3 genomes AF: 0.0593 AC: 9024 AN: 152096 Hom.: 313 Cov.: 32

Gnomad AFR AF: 0.0805

Gnomad AMI AF: 0.0516

Gnomad AMR AF: 0.0533

Gnomad ASJ AF: 0.0701

Gnomad EAS AF: 0.0962

Gnomad SAS AF: 0.0603

Gnomad FIN AF: 0.0264

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0494

Gnomad OTH AF: 0.0602

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0594 AC: 9040 AN: 152214 Hom.: 316 Cov.: 32 AF XY: 0.0589 AC XY: 4386 AN XY: 74430

Gnomad4 AFR AF: 0.0806

Gnomad4 AMR AF: 0.0531

Gnomad4 ASJ AF: 0.0701

Gnomad4 EAS AF: 0.0970

Gnomad4 SAS AF: 0.0612

Gnomad4 FIN AF: 0.0264

Gnomad4 NFE AF: 0.0494

Gnomad4 OTH AF: 0.0591

Alfa AF: 0.0489 Hom.: 277

Bravo AF: 0.0637

Asia WGS AF: 0.0680 AC: 235 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	10
Dann	Benign	0.90

Splicing

Name	Calibrated prediction	Score	Prediction
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

Publications

LitVar

Other links and lift over

dbSNP: rs11999298; hg19: chr9-36894151;