Genetic Variant PAX7:c.587-5467G>A (chr1-18686287-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001135254.2(PAX7):c.587-5467G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.933 in 152,290 control chromosomes in the GnomAD database, including 66,434 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 0.93 ( 66434 hom., cov: 32)

Consequence

PAX7
NM_001135254.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.638

Publications

2 publications found

Variant links:

Genes affected

PAX7 (HGNC:8621): (paired box 7) This gene is a member of the paired box (PAX) family of transcription factors. Members of this gene family typically contain a paired box domain, an octapeptide, and a paired-type homeodomain. These genes play critical roles during fetal development and cancer growth. The specific function of the paired box 7 gene is unknown but speculated to involve tumor suppression since fusion of this gene with a forkhead domain family member has been associated with alveolar rhabdomyosarcoma. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2008]

PAX7 Gene-Disease associations (from GenCC):

myopathy, congenital, progressive, with scoliosis
Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Illumina
congenital myopathy with myasthenic-like onset
Inheritance: AR Classification: MODERATE Submitted by: ClinGen

PAX7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PAX7	NM_001135254.2 link	c.587-5467G>A	intron_variant	Intron 4 of 8	ENST00000420770.7	NP_001128726.1	P23759-3
PAX7	NM_002584.3 link	c.587-5467G>A	intron_variant	Intron 4 of 7		NP_002575.1	P23759-1
PAX7	NM_013945.3 link	c.581-5467G>A	intron_variant	Intron 4 of 7		NP_039236.1	P23759-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAX7	ENST00000420770.7 link	c.587-5467G>A		intron_variant	Intron 4 of 8	1	NM_001135254.2	ENSP00000403389.2		P23759-3

Frequencies

GnomAD3 genomes

AF:

0.932

AC:

141893

AN:

152172

Hom.:

66365

Cov.:

show subpopulations

Gnomad AFR

AF:

0.979

Gnomad AMI

AF:

0.966

Gnomad AMR

AF:

0.927

Gnomad ASJ

AF:

0.865

Gnomad EAS

AF:

0.702

Gnomad SAS

AF:

0.888

Gnomad FIN

AF:

0.904

Gnomad MID

AF:

0.889

Gnomad NFE

AF:

0.934

Gnomad OTH

AF:

0.929

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

GnomAD4 genome

AF:

0.933

AC:

142021

AN:

152290

Hom.:

66434

Cov.:

AF XY:

0.929

AC XY:

69172

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.979

AC:

40695

AN:

41566

American (AMR)

AF:

0.927

AC:

14180

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.865

AC:

3000

AN:

3470

East Asian (EAS)

AF:

0.702

AC:

3633

AN:

5178

South Asian (SAS)

AF:

0.890

AC:

4283

AN:

4814

European-Finnish (FIN)

AF:

0.904

AC:

9596

AN:

10612

Middle Eastern (MID)

AF:

0.898

AC:

264

AN:

294

European-Non Finnish (NFE)

AF:

0.934

AC:

63524

AN:

68030

Other (OTH)

AF:

0.930

AC:

1965

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

493

986

1478

1971

2464

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

906

1812

2718

3624

4530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.925

Hom.:

66527

Bravo

AF:

0.934

Asia WGS

AF:

0.814

AC:

2831

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.26

(source)

DANN

Benign

0.18

PhyloP100

-0.64

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over