chr1-18718383-C-T

Variant names:

• chr1-18718383-C-T
• rs624761
• NM_001135254.2:c.1155+15087C>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.1155+15087C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 152,086 control chromosomes in the GnomAD database, including 49,389 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 0.81 (49389 hom., cov: 31)
• Consequence: PAX7 NM_001135254.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0430
• Publications: 11 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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAX7	NM_001135254.2	c.1155+15087C>T		intron_variant	Intron 7 of 8	ENST00000420770.7	NP_001128726.1
PAX7	NM_002584.3	c.1155+15087C>T		intron_variant	Intron 7 of 7		NP_002575.1
PAX7	NM_013945.3	c.1149+15087C>T		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+15087C>T		intron_variant	Intron 7 of 8	1	NM_001135254.2	ENSP00000403389.2

Frequencies

GnomAD3 genomes AF: 0.806 AC: 122474 AN: 151968 Hom.: 49352 Cov.: 31

Gnomad AFR AF: 0.807

Gnomad AMI AF: 0.890

Gnomad AMR AF: 0.789

Gnomad ASJ AF: 0.703

Gnomad EAS AF: 0.825

Gnomad SAS AF: 0.833

Gnomad FIN AF: 0.854

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.802

Gnomad OTH AF: 0.816

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

GnomAD4 genome AF: 0.806 AC: 122568 AN: 152086 Hom.: 49389 Cov.: 31 AF XY: 0.810 AC XY: 60206 AN XY: 74354

African (AFR) AF: 0.807 AC: 33469 AN: 41462

American (AMR) AF: 0.789 AC: 12063 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.703 AC: 2440 AN: 3470

East Asian (EAS) AF: 0.825 AC: 4252 AN: 5154

South Asian (SAS) AF: 0.833 AC: 4008 AN: 4812

European-Finnish (FIN) AF: 0.854 AC: 9047 AN: 10594

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.802 AC: 54521 AN: 67992

Other (OTH) AF: 0.812 AC: 1715 AN: 2112

Alfa AF: 0.795 Hom.: 93720

Bravo AF: 0.798

Asia WGS AF: 0.794 AC: 2758 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.7
DANN	Benign	0.26
PhyloP100		0.043
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: rs624761; hg19: chr1-19044877;