rs712704

chr7-127618154-G-Achr7-127618154-G-Cchr7-127618154-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The 7-127618154-G-A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.81 in 152,554 control chromosomes in the GnomAD database, including 51,059 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 0.81 (50934 hom., cov: 32)
  • Exomes 𝑓: 0.80 (125 hom.)
• Consequence: PAX4 NM_001366110.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14

Genes affected

PAX4 (HGNC:8618): (paired box 4) 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 paired box 4 gene is involved in pancreatic islet development and mouse studies have demonstrated a role for this gene in differentiation of insulin-producing beta cells. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAX4	NM_001366110.1			upstream_gene_variant		ENST00000639438.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAX4	ENST00000639438.3			upstream_gene_variant		5	NM_001366110.1	A2

Frequencies

GnomAD3 genomes AF: 0.810 AC: 123154 AN: 152058 Hom.: 50882 Cov.: 32

Gnomad AFR AF: 0.943

Gnomad AMI AF: 0.797

Gnomad AMR AF: 0.781

Gnomad ASJ AF: 0.885

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.741

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.784

Gnomad OTH AF: 0.806

GnomAD4 exome AF: 0.804 AC: 304 AN: 378 Hom.: 125 Cov.: 0 AF XY: 0.791 AC XY: 234 AN XY: 296

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.563

Gnomad4 NFE exome AF: 0.812

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.810 AC: 123262 AN: 152176 Hom.: 50934 Cov.: 32 AF XY: 0.802 AC XY: 59641 AN XY: 74388

Gnomad4 AFR AF: 0.943

Gnomad4 AMR AF: 0.781

Gnomad4 ASJ AF: 0.885

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.740

Gnomad4 FIN AF: 0.718

Gnomad4 NFE AF: 0.784

Gnomad4 OTH AF: 0.804

Alfa AF: 0.793 Hom.: 10732

Bravo AF: 0.821

Asia WGS AF: 0.601 AC: 2093 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
Cadd	Benign	18
Dann	Benign	0.67

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs712704; hg19: chr7-127258208;