dbSNP rs2236835: PAX7:c.586+27386G>A (chr1-18663757-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.586+27386G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0306 in 152,352 control chromosomes in the GnomAD database, including 132 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 0.031 ( 132 hom., cov: 33)

Consequence

PAX7
NM_001135254.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.616

Publications

6 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=-0.85).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PAX7	NM_001135254.2 link	c.586+27386G>A	intron_variant	Intron 4 of 8	ENST00000420770.7	NP_001128726.1	P23759-3
PAX7	NM_002584.3 link	c.586+27386G>A	intron_variant	Intron 4 of 7		NP_002575.1	P23759-1
PAX7	NM_013945.3 link	c.580+27386G>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.586+27386G>A		intron_variant	Intron 4 of 8	1	NM_001135254.2	ENSP00000403389.2		P23759-3

Frequencies

GnomAD3 genomes

AF:

0.0306

AC:

4662

AN:

152234

Hom.:

130

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00781

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0508

Gnomad ASJ

AF:

0.0132

Gnomad EAS

AF:

0.0736

Gnomad SAS

AF:

0.114

Gnomad FIN

AF:

0.00753

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0359

Gnomad OTH

AF:

0.0282

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

GnomAD4 genome

AF:

0.0306

AC:

4669

AN:

152352

Hom.:

132

Cov.:

AF XY:

0.0318

AC XY:

2371

AN XY:

74506

show subpopulations

African (AFR)

AF:

0.00779

AC:

324

AN:

41586

American (AMR)

AF:

0.0507

AC:

776

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0132

AC:

AN:

3472

East Asian (EAS)

AF:

0.0738

AC:

383

AN:

5192

South Asian (SAS)

AF:

0.114

AC:

551

AN:

4826

European-Finnish (FIN)

AF:

0.00753

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0359

AC:

2442

AN:

68028

Other (OTH)

AF:

0.0308

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

231

462

692

923

1154

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

198

264

330

<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:

0.0341

Hom.:

243

Bravo

AF:

0.0316

Asia WGS

AF:

0.0950

AC:

330

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.1

(source)

DANN

Benign

0.95

PhyloP100

-0.62

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

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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