Variant 9-36840709-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_016734.3(PAX5):c.1100-73G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0022 in 903,242 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0082 ( 16 hom., cov: 33)

Exomes 𝑓: 0.00097 ( 14 hom. )

Consequence

PAX5
NM_016734.3 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.496

Variant links:

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]

PAX5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 9-36840709-C-A is Benign according to our data. Variant chr9-36840709-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1254224.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00825 (1256/152272) while in subpopulation AFR AF= 0.0281 (1166/41536). AF 95% confidence interval is 0.0267. There are 16 homozygotes in gnomad4. There are 610 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1256 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAX5	NM_016734.3 linkuse as main transcript	c.1100-73G>T		intron_variant		ENST00000358127.9	NP_057953.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAX5	ENST00000358127.9 linkuse as main transcript	c.1100-73G>T		intron_variant		1	NM_016734.3	ENSP00000350844	P1	Q02548-1

Frequencies

GnomAD3 genomes

AF:

0.00825

AC:

1256

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0281

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00445

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00767

GnomAD4 exome

AF:

0.000969

AC:

728

AN:

750970

Hom.:

AF XY:

0.000795

AC XY:

305

AN XY:

383648

show subpopulations

Gnomad4 AFR exome

AF:

0.0281

Gnomad4 AMR exome

AF:

0.000961

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000356

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000463

Gnomad4 OTH exome

AF:

0.00211

GnomAD4 genome

AF:

0.00825

AC:

1256

AN:

152272

Hom.:

Cov.:

AF XY:

0.00819

AC XY:

610

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0281

Gnomad4 AMR

AF:

0.00444

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00759

Alfa

AF:

0.00638

Hom.:

Bravo

AF:

0.00854

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.2

DANN

Benign

0.85

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over