chr9-36840647-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_016734.3(PAX5):​c.1100-11G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00095 in 1,537,074 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00089 ( 16 hom. )

Consequence

PAX5
NM_016734.3 splice_polypyrimidine_tract, intron

Scores

2
Splicing: ADA: 0.0001408
2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.50
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.73).
BP6
Variant 9-36840647-C-T is Benign according to our data. Variant chr9-36840647-C-T is described in ClinVar as [Benign]. Clinvar id is 1336248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00154 (234/152232) while in subpopulation SAS AF= 0.0108 (52/4820). AF 95% confidence interval is 0.00845. There are 1 homozygotes in gnomad4. There are 108 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 234 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PAX5NM_016734.3 linkuse as main transcriptc.1100-11G>A splice_polypyrimidine_tract_variant, intron_variant ENST00000358127.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PAX5ENST00000358127.9 linkuse as main transcriptc.1100-11G>A splice_polypyrimidine_tract_variant, intron_variant 1 NM_016734.3 P1Q02548-1

Frequencies

GnomAD3 genomes
AF:
0.00153
AC:
233
AN:
152114
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00401
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000589
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.0110
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.00199
AC:
319
AN:
160532
Hom.:
3
AF XY:
0.00241
AC XY:
204
AN XY:
84676
show subpopulations
Gnomad AFR exome
AF:
0.00352
Gnomad AMR exome
AF:
0.000162
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0123
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000620
Gnomad OTH exome
AF:
0.000451
GnomAD4 exome
AF:
0.000885
AC:
1226
AN:
1384842
Hom.:
16
Cov.:
25
AF XY:
0.00119
AC XY:
813
AN XY:
684222
show subpopulations
Gnomad4 AFR exome
AF:
0.00355
Gnomad4 AMR exome
AF:
0.000223
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000266
Gnomad4 SAS exome
AF:
0.0123
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000470
Gnomad4 OTH exome
AF:
0.00135
GnomAD4 genome
AF:
0.00154
AC:
234
AN:
152232
Hom.:
1
Cov.:
33
AF XY:
0.00145
AC XY:
108
AN XY:
74442
show subpopulations
Gnomad4 AFR
AF:
0.00405
Gnomad4 AMR
AF:
0.000588
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.0108
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.000516
Hom.:
0
Bravo
AF:
0.00143
Asia WGS
AF:
0.00462
AC:
16
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoMay 28, 2019- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 03, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.73
CADD
Benign
0.087
DANN
Benign
0.85

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00014
dbscSNV1_RF
Benign
0.014
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.

Other links and lift over

dbSNP: rs149896434; hg19: chr9-36840644; API