1-18657203-G-A

Variant names:

• chr1-18657203-G-A
• rs6659735
• NM_001135254.2:c.586+20832G>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.586+20832G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 151,656 control chromosomes in the GnomAD database, including 10,010 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 0.36 (10010 hom., cov: 30)
• Consequence: PAX7 NM_001135254.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.445
• Publications: 5 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 (NFE) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAX7	NM_001135254.2	c.586+20832G>A		intron_variant	Intron 4 of 8	ENST00000420770.7	NP_001128726.1
PAX7	NM_002584.3	c.586+20832G>A		intron_variant	Intron 4 of 7		NP_002575.1
PAX7	NM_013945.3	c.580+20832G>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.586+20832G>A		intron_variant	Intron 4 of 8	1	NM_001135254.2	ENSP00000403389.2

Frequencies

GnomAD3 genomes AF: 0.356 AC: 53882 AN: 151536 Hom.: 10013 Cov.: 30

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.0382

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.355 AC: 53892 AN: 151656 Hom.: 10010 Cov.: 30 AF XY: 0.356 AC XY: 26406 AN XY: 74090

African (AFR) AF: 0.340 AC: 14055 AN: 41338

American (AMR) AF: 0.286 AC: 4368 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 1064 AN: 3462

East Asian (EAS) AF: 0.0381 AC: 195 AN: 5122

South Asian (SAS) AF: 0.272 AC: 1302 AN: 4792

European-Finnish (FIN) AF: 0.473 AC: 4973 AN: 10504

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.396 AC: 26913 AN: 67880

Other (OTH) AF: 0.349 AC: 734 AN: 2106

Alfa AF: 0.470 Hom.: 32620

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.42
DANN	Benign	0.46
PhyloP100		-0.45
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: rs6659735; hg19: chr1-18983697;