1-18663757-G-A

Position:

• chr1-18663757-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001135254.2(PAX7):​c.586+27386G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0306 in 152,352 control chromosomes in the GnomAD database, including 132 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 0.031 (132 hom., cov: 33)
• Consequence: PAX7 NM_001135254.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.616

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAX7	NM_001135254.2	c.586+27386G>A		intron_variant		ENST00000420770.7	NP_001128726.1
PAX7	NM_002584.3	c.586+27386G>A		intron_variant			NP_002575.1
PAX7	NM_013945.3	c.580+27386G>A		intron_variant			NP_039236.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAX7	ENST00000420770.7	c.586+27386G>A		intron_variant		1	NM_001135254.2	ENSP00000403389.2
PAX7	ENST00000375375.7	c.586+27386G>A		intron_variant		1		ENSP00000364524.3
PAX7	ENST00000400661.3	c.580+27386G>A		intron_variant		1		ENSP00000383502.3

Frequencies

GnomAD3 genomes AF: 0.0306 AC: 4662 AN: 152234 Hom.: 130 Cov.: 33

Gnomad AFR AF: 0.00781

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0508

Gnomad ASJ AF: 0.0132

Gnomad EAS AF: 0.0736

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.00753

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0359

Gnomad OTH AF: 0.0282

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

GnomAD4 genome AF: 0.0306 AC: 4669 AN: 152352 Hom.: 132 Cov.: 33 AF XY: 0.0318 AC XY: 2371 AN XY: 74506

Gnomad4 AFR AF: 0.00779

Gnomad4 AMR AF: 0.0507

Gnomad4 ASJ AF: 0.0132

Gnomad4 EAS AF: 0.0738

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.00753

Gnomad4 NFE AF: 0.0359

Gnomad4 OTH AF: 0.0308

Alfa AF: 0.0356 Hom.: 164

Bravo AF: 0.0316

Asia WGS AF: 0.0950 AC: 330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.1
DANN	Benign	0.95

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

Publications

LitVar

Other links and lift over

dbSNP: rs2236835; hg19: chr1-18990251;