rs2236805

Variant names:

• chr1-18731236-G-A
• rs2236805
• NM_001135254.2:c.1156-4396G>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.1156-4396G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 152,086 control chromosomes in the GnomAD database, including 8,743 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 0.33 (8743 hom., cov: 32)
• Consequence: PAX7 NM_001135254.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.400
• Publications: 4 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.392 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.1156-4396G>A		intron	N/A	NP_001128726.1
	PAX7	NM_002584.3		c.1156-4396G>A		intron	N/A	NP_002575.1
	PAX7	NM_013945.3		c.1150-4396G>A		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.1156-4396G>A		intron	N/A	ENSP00000403389.2
	PAX7	ENST00000375375.7	TSL:1	c.1156-4396G>A		intron	N/A	ENSP00000364524.3
	PAX7	ENST00000400661.3	TSL:1	c.1150-4396G>A		intron	N/A	ENSP00000383502.3

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49510 AN: 151968 Hom.: 8746 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.326 AC: 49522 AN: 152086 Hom.: 8743 Cov.: 32 AF XY: 0.325 AC XY: 24180 AN XY: 74332

African (AFR) AF: 0.194 AC: 8055 AN: 41506

American (AMR) AF: 0.295 AC: 4508 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1724 AN: 3466

East Asian (EAS) AF: 0.229 AC: 1176 AN: 5146

South Asian (SAS) AF: 0.379 AC: 1826 AN: 4820

European-Finnish (FIN) AF: 0.385 AC: 4066 AN: 10568

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.396 AC: 26944 AN: 67976

Other (OTH) AF: 0.356 AC: 752 AN: 2114

Alfa AF: 0.384 Hom.: 19421

Bravo AF: 0.314

Asia WGS AF: 0.293 AC: 1018 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.2
DANN	Benign	0.69
PhyloP100		0.40
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: rs2236805; hg19: chr1-19057730; COSMIC: COSV64753250;