1-18635197-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BS1 BS2

The NM_001135254.2(PAX7):c.408G>A(p.Arg136=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000983 in 1,614,016 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0050 (5 hom., cov: 32)
  • Exomes 𝑓: 0.00056 (7 hom.)
• Consequence: PAX7 NM_001135254.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.61

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 1-18635197-G-A is Benign according to our data. Variant chr1-18635197-G-A is described in ClinVar as [Benign]. Clinvar id is 775519.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.61 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00502 (764/152298) while in subpopulation AFR AF= 0.0168 (699/41556). AF 95% confidence interval is 0.0158. There are 5 homozygotes in gnomad4. There are 374 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAX7	NM_001135254.2	c.408G>A	p.Arg136=	synonymous_variant	3/9	ENST00000420770.7
PAX7	NM_002584.3	c.408G>A	p.Arg136=	synonymous_variant	3/8
PAX7	NM_013945.3	c.408G>A	p.Arg136=	synonymous_variant	3/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAX7	ENST00000420770.7	c.408G>A	p.Arg136=	synonymous_variant	3/9	1	NM_001135254.2	P1
PAX7	ENST00000375375.7	c.408G>A	p.Arg136=	synonymous_variant	3/8	1
PAX7	ENST00000400661.3	c.408G>A	p.Arg136=	synonymous_variant	3/8	1

Frequencies

GnomAD3 genomes AF: 0.00504 AC: 767 AN: 152180 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.0169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00860

GnomAD3 exomes AF: 0.00151 AC: 380 AN: 251368 Hom.: 5 AF XY: 0.00124 AC XY: 169 AN XY: 135880

Gnomad AFR exome AF: 0.0180

Gnomad AMR exome AF: 0.00179

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000150

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.000563 AC: 823 AN: 1461718 Hom.: 7 Cov.: 31 AF XY: 0.000513 AC XY: 373 AN XY: 727162

Gnomad4 AFR exome AF: 0.0176

Gnomad4 AMR exome AF: 0.00170

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000585

Gnomad4 OTH exome AF: 0.00139

GnomAD4 genome AF: 0.00502 AC: 764 AN: 152298 Hom.: 5 Cov.: 32 AF XY: 0.00502 AC XY: 374 AN XY: 74466

Gnomad4 AFR AF: 0.0168

Gnomad4 AMR AF: 0.00274

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00851

Alfa AF: 0.00362 Hom.: 0

Bravo AF: 0.00575

Asia WGS AF: 0.00202 AC: 8 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
Cadd	Benign	8.4
Dann	Benign	0.70

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: rs72937282; hg19: chr1-18961691;