NM_001135254.2:c.587-5467G>A

Variant names:

• chr1-18686287-G-A
• rs553934
• NM_001135254.2:c.587-5467G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.638
• Publications: 2 publications found

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

ACMG classification

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.932 AC: 141893 AN: 152172 Hom.: 66365 Cov.: 32

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.: 32 AF XY: 0.929 AC XY: 69172 AN XY: 74470

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

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
DANN	Benign	0.18
PhyloP100		-0.64
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs553934; hg19: chr1-19012781;