1-18653380-G-T

Position:

• chr1-18653380-G-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.91).
• 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/exons	MANE	Protein	UniProt
PAX7	NM_001135254.2	c.586+17009G>T		intron_variant		ENST00000420770.7	NP_001128726.1
PAX7	NM_002584.3	c.586+17009G>T		intron_variant			NP_002575.1
PAX7	NM_013945.3	c.580+17009G>T		intron_variant			NP_039236.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAX7	ENST00000420770.7	c.586+17009G>T		intron_variant		1	NM_001135254.2	ENSP00000403389	P1
PAX7	ENST00000375375.7	c.586+17009G>T		intron_variant		1		ENSP00000364524
PAX7	ENST00000400661.3	c.580+17009G>T		intron_variant		1		ENSP00000383502

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

Gnomad4 AFR AF: 0.403

Gnomad4 AMR AF: 0.324

Gnomad4 ASJ AF: 0.353

Gnomad4 EAS AF: 0.0383

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.482

Gnomad4 NFE AF: 0.415

Gnomad4 OTH AF: 0.392

Alfa AF: 0.396 Hom.: 6443

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

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: rs742071; hg19: chr1-18979874;