rs2236805

chr1-18731236-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.1156-4396G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 152,086 control chromosomes in the GnomAD database, including 8,743 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 0.33 (8743 hom., cov: 32)
• Consequence: PAX7 NM_001135254.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.400

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAX7	NM_001135254.2	c.1156-4396G>A		intron_variant		ENST00000420770.7
PAX7	NM_002584.3	c.1156-4396G>A		intron_variant
PAX7	NM_013945.3	c.1150-4396G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAX7	ENST00000420770.7	c.1156-4396G>A		intron_variant		1	NM_001135254.2	P1
PAX7	ENST00000375375.7	c.1156-4396G>A		intron_variant		1
PAX7	ENST00000400661.3	c.1150-4396G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49510 AN: 151968 Hom.: 8746 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.326 AC: 49522 AN: 152086 Hom.: 8743 Cov.: 32 AF XY: 0.325 AC XY: 24180 AN XY: 74332

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.497

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.379

Gnomad4 FIN AF: 0.385

Gnomad4 NFE AF: 0.396

Gnomad4 OTH AF: 0.356

Alfa AF: 0.391 Hom.: 15709

Bravo AF: 0.314

Asia WGS AF: 0.293 AC: 1018 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	9.2
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: rs2236805; hg19: chr1-19057730; COSMIC: COSV64753250;