rs742071

Variant names:

• chr1-18653380-G-T
• rs742071
• NM_001135254.2:c.586+17009G>T

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+17009G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 151,852 control chromosomes in the GnomAD database, including 11,811 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 (11811 hom., cov: 31)
• Consequence: PAX7 NM_001135254.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.21
• Publications: 33 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAX7	NM_001135254.2	c.586+17009G>T		intron_variant	Intron 4 of 8	ENST00000420770.7	NP_001128726.1
PAX7	NM_002584.3	c.586+17009G>T		intron_variant	Intron 4 of 7		NP_002575.1
PAX7	NM_013945.3	c.580+17009G>T		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+17009G>T		intron_variant	Intron 4 of 8	1	NM_001135254.2	ENSP00000403389.2

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58761 AN: 151734 Hom.: 11809 Cov.: 31

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.0384

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.394

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

GnomAD4 genome AF: 0.387 AC: 58787 AN: 151852 Hom.: 11811 Cov.: 31 AF XY: 0.388 AC XY: 28754 AN XY: 74202

African (AFR) AF: 0.403 AC: 16685 AN: 41380

American (AMR) AF: 0.324 AC: 4947 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 1225 AN: 3466

East Asian (EAS) AF: 0.0383 AC: 198 AN: 5176

South Asian (SAS) AF: 0.277 AC: 1334 AN: 4810

European-Finnish (FIN) AF: 0.482 AC: 5073 AN: 10526

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.415 AC: 28162 AN: 67934

Other (OTH) AF: 0.392 AC: 823 AN: 2102

Alfa AF: 0.395 Hom.: 24989

Bravo AF: 0.372

Asia WGS AF: 0.155 AC: 542 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.032
DANN	Benign	0.69
PhyloP100		-2.2
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: rs742071; hg19: chr1-18979874;