rs880810

Variant names:

• chr1-18668060-C-G
• rs880810
• NM_001135254.2:c.587-23694C>G

Variant summary

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

The NM_001135254.2(PAX7):​c.587-23694C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0937 in 152,116 control chromosomes in the GnomAD database, including 735 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 0.094 (735 hom., cov: 32)
• Consequence: PAX7 NM_001135254.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.308
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAX7	NM_001135254.2	c.587-23694C>G		intron_variant	Intron 4 of 8	ENST00000420770.7	NP_001128726.1
PAX7	NM_002584.3	c.587-23694C>G		intron_variant	Intron 4 of 7		NP_002575.1
PAX7	NM_013945.3	c.581-23694C>G		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.587-23694C>G		intron_variant	Intron 4 of 8	1	NM_001135254.2	ENSP00000403389.2

Frequencies

GnomAD3 genomes AF: 0.0937 AC: 14243 AN: 151996 Hom.: 727 Cov.: 32

Gnomad AFR AF: 0.0556

Gnomad AMI AF: 0.0670

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.0955

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.0870

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

GnomAD4 genome AF: 0.0937 AC: 14260 AN: 152116 Hom.: 735 Cov.: 32 AF XY: 0.0946 AC XY: 7032 AN XY: 74326

African (AFR) AF: 0.0556 AC: 2307 AN: 41514

American (AMR) AF: 0.127 AC: 1932 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 366 AN: 3472

East Asian (EAS) AF: 0.135 AC: 696 AN: 5166

South Asian (SAS) AF: 0.124 AC: 597 AN: 4806

European-Finnish (FIN) AF: 0.101 AC: 1064 AN: 10580

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 7030 AN: 67996

Other (OTH) AF: 0.0847 AC: 179 AN: 2114

Alfa AF: 0.107 Hom.: 128

Bravo AF: 0.0950

Asia WGS AF: 0.118 AC: 410 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.8
DANN	Benign	0.43
PhyloP100		-0.31
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: rs880810; hg19: chr1-18994554;