1-18705778-G-C

Variant names:

• chr1-18705778-G-C
• rs2236824
• NM_001135254.2:c.1155+2482G>C

Variant summary

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

The NM_001135254.2(PAX7):​c.1155+2482G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 152,024 control chromosomes in the GnomAD database, including 12,308 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 (12308 hom., cov: 31)
• Consequence: PAX7 NM_001135254.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAX7	NM_001135254.2	c.1155+2482G>C		intron_variant	Intron 7 of 8	ENST00000420770.7	NP_001128726.1
PAX7	NM_002584.3	c.1155+2482G>C		intron_variant	Intron 7 of 7		NP_002575.1
PAX7	NM_013945.3	c.1149+2482G>C		intron_variant	Intron 7 of 7		NP_039236.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAX7	ENST00000420770.7	c.1155+2482G>C		intron_variant	Intron 7 of 8	1	NM_001135254.2	ENSP00000403389.2

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59175 AN: 151906 Hom.: 12292 Cov.: 31

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.380

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

GnomAD4 genome AF: 0.390 AC: 59223 AN: 152024 Hom.: 12308 Cov.: 31 AF XY: 0.390 AC XY: 29009 AN XY: 74316

African (AFR) AF: 0.254 AC: 10517 AN: 41484

American (AMR) AF: 0.368 AC: 5623 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1204 AN: 3468

East Asian (EAS) AF: 0.249 AC: 1281 AN: 5150

South Asian (SAS) AF: 0.452 AC: 2177 AN: 4818

European-Finnish (FIN) AF: 0.510 AC: 5394 AN: 10576

Middle Eastern (MID) AF: 0.390 AC: 114 AN: 292

European-Non Finnish (NFE) AF: 0.466 AC: 31685 AN: 67944

Other (OTH) AF: 0.378 AC: 798 AN: 2112

Alfa AF: 0.289 Hom.: 786

Bravo AF: 0.371

Asia WGS AF: 0.346 AC: 1202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.41
DANN	Benign	0.48
PhyloP100		-1.5
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: rs2236824; hg19: chr1-19032272;