1-18703052-A-G

Variant names:

• chr1-18703052-A-G
• rs1416464
• NM_001135254.2:c.953-42A>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.953-42A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 1,570,530 control chromosomes in the GnomAD database, including 80,130 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 0.39 (12878 hom., cov: 33)
  • Exomes 𝑓: 0.29 (67252 hom.)
• Consequence: PAX7 NM_001135254.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.419
• Publications: 7 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135254.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAX7	NM_001135254.2	MANE Select	c.953-42A>G		intron	N/A	NP_001128726.1
	PAX7	NM_002584.3		c.953-42A>G		intron	N/A	NP_002575.1
	PAX7	NM_013945.3		c.947-42A>G		intron	N/A	NP_039236.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAX7	ENST00000420770.7	TSL:1 MANE Select	c.953-42A>G		intron	N/A	ENSP00000403389.2
	PAX7	ENST00000375375.7	TSL:1	c.953-42A>G		intron	N/A	ENSP00000364524.3
	PAX7	ENST00000400661.3	TSL:1	c.947-42A>G		intron	N/A	ENSP00000383502.3

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58585 AN: 151910 Hom.: 12853 Cov.: 33

Gnomad AFR AF: 0.588

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.602

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.374

GnomAD2 exomes AF: 0.370 AC: 89162 AN: 241200 AF XY: 0.361

Gnomad AFR exome AF: 0.594

Gnomad AMR exome AF: 0.467

Gnomad ASJ exome AF: 0.394

Gnomad EAS exome AF: 0.603

Gnomad FIN exome AF: 0.323

Gnomad NFE exome AF: 0.267

Gnomad OTH exome AF: 0.334

GnomAD4 exome AF: 0.293 AC: 416227 AN: 1418502 Hom.: 67252 Cov.: 27 AF XY: 0.295 AC XY: 207783 AN XY: 703646

African (AFR) AF: 0.598 AC: 19450 AN: 32530

American (AMR) AF: 0.454 AC: 19920 AN: 43838

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 10049 AN: 25612

East Asian (EAS) AF: 0.584 AC: 22843 AN: 39110

South Asian (SAS) AF: 0.396 AC: 33781 AN: 85202

European-Finnish (FIN) AF: 0.325 AC: 17067 AN: 52502

Middle Eastern (MID) AF: 0.311 AC: 1498 AN: 4822

European-Non Finnish (NFE) AF: 0.253 AC: 272445 AN: 1076374

Other (OTH) AF: 0.328 AC: 19174 AN: 58512

GnomAD4 genome AF: 0.386 AC: 58661 AN: 152028 Hom.: 12878 Cov.: 33 AF XY: 0.386 AC XY: 28687 AN XY: 74320

African (AFR) AF: 0.588 AC: 24399 AN: 41466

American (AMR) AF: 0.379 AC: 5787 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1370 AN: 3466

East Asian (EAS) AF: 0.601 AC: 3094 AN: 5148

South Asian (SAS) AF: 0.404 AC: 1947 AN: 4822

European-Finnish (FIN) AF: 0.315 AC: 3329 AN: 10578

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.258 AC: 17519 AN: 67954

Other (OTH) AF: 0.376 AC: 794 AN: 2110

Alfa AF: 0.339 Hom.: 4328

Bravo AF: 0.403

Asia WGS AF: 0.507 AC: 1763 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.53
PhyloP100		-0.42
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: rs1416464; hg19: chr1-19029546; COSMIC: COSV64751228;