rs618941

Positions:

• chr1-18679658-G-A
• chr1-18679658-G-C

Variant summary

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

The NM_001135254.2(PAX7):​c.587-12096G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.903 in 152,210 control chromosomes in the GnomAD database, including 62,221 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 0.90 (62221 hom., cov: 32)
• Consequence: PAX7 NM_001135254.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAX7	NM_001135254.2	c.587-12096G>A		intron_variant		ENST00000420770.7	NP_001128726.1
PAX7	NM_002584.3	c.587-12096G>A		intron_variant			NP_002575.1
PAX7	NM_013945.3	c.581-12096G>A		intron_variant			NP_039236.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAX7	ENST00000420770.7	c.587-12096G>A		intron_variant		1	NM_001135254.2	ENSP00000403389	P1
PAX7	ENST00000375375.7	c.587-12096G>A		intron_variant		1		ENSP00000364524
PAX7	ENST00000400661.3	c.581-12096G>A		intron_variant		1		ENSP00000383502

Frequencies

GnomAD3 genomes AF: 0.903 AC: 137286 AN: 152092 Hom.: 62164 Cov.: 32

Gnomad AFR AF: 0.898

Gnomad AMI AF: 0.963

Gnomad AMR AF: 0.916

Gnomad ASJ AF: 0.867

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.882

Gnomad FIN AF: 0.868

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.929

Gnomad OTH AF: 0.904

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

GnomAD4 genome AF: 0.903 AC: 137401 AN: 152210 Hom.: 62221 Cov.: 32 AF XY: 0.898 AC XY: 66822 AN XY: 74394

Gnomad4 AFR AF: 0.897

Gnomad4 AMR AF: 0.916

Gnomad4 ASJ AF: 0.867

Gnomad4 EAS AF: 0.664

Gnomad4 SAS AF: 0.883

Gnomad4 FIN AF: 0.868

Gnomad4 NFE AF: 0.929

Gnomad4 OTH AF: 0.905

Alfa AF: 0.921 Hom.: 83229

Bravo AF: 0.904

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.51
DANN	Benign	0.41

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: rs618941; hg19: chr1-19006152;