rs2233575

chr7-127615819-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001366110.1(PAX4):c.13+97G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00156 in 1,531,800 control chromosomes in the GnomAD database, including 92 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 0.0024 (15 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (77 hom.)
• Consequence: PAX4 NM_001366110.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00243 (370/152304) while in subpopulation EAS AF= 0.0551 (285/5172). AF 95% confidence interval is 0.0498. There are 15 homozygotes in gnomad4. There are 180 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 364 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAX4	NM_001366110.1	c.13+97G>A		intron_variant		ENST00000639438.3
PAX4	NM_001366111.1	c.13+97G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAX4	ENST00000639438.3	c.13+97G>A		intron_variant		5	NM_001366110.1	A2
PAX4	ENST00000378740.6	c.13+97G>A		intron_variant		1		P2

Frequencies

GnomAD3 genomes AF: 0.00239 AC: 364 AN: 152186 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.000627

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0546

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00670

GnomAD4 exome AF: 0.00146 AC: 2018 AN: 1379496 Hom.: 77 Cov.: 30 AF XY: 0.00143 AC XY: 972 AN XY: 680554

Gnomad4 AFR exome AF: 0.000318

Gnomad4 AMR exome AF: 0.0000563

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0409

Gnomad4 SAS exome AF: 0.00115

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000186

Gnomad4 OTH exome AF: 0.00754

GnomAD4 genome AF: 0.00243 AC: 370 AN: 152304 Hom.: 15 Cov.: 32 AF XY: 0.00242 AC XY: 180 AN XY: 74466

Gnomad4 AFR AF: 0.000626

Gnomad4 AMR AF: 0.00170

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0551

Gnomad4 SAS AF: 0.00186

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00852

Alfa AF: 0.000902 Hom.: 0

Bravo AF: 0.00258

Asia WGS AF: 0.0320 AC: 112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	9.6
Dann	Benign	0.52

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2233575; hg19: chr7-127255873; COSMIC: COSV58390710; COSMIC: COSV58390710;