rs327518

Positions:

• chr7-127611738-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001366110.1(PAX4):​c.772-62C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 1,601,966 control chromosomes in the GnomAD database, including 117,809 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.30 (8438 hom., cov: 32)
  • Exomes 𝑓: 0.38 (109371 hom.)
• Consequence: PAX4 NM_001366110.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.09

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 7-127611738-G-A is Benign according to our data. Variant chr7-127611738-G-A is described in ClinVar as [Benign]. Clinvar id is 1292426.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAX4	NM_001366110.1	c.772-62C>T		intron_variant		ENST00000639438.3
PAX4	NM_001366111.1	c.772-62C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAX4	ENST00000639438.3	c.772-62C>T		intron_variant		5	NM_001366110.1	A2

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46075 AN: 151862 Hom.: 8432 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.100

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.340

GnomAD4 exome AF: 0.381 AC: 551964 AN: 1450006 Hom.: 109371 Cov.: 49 AF XY: 0.379 AC XY: 273315 AN XY: 721532

Gnomad4 AFR exome AF: 0.105

Gnomad4 AMR exome AF: 0.442

Gnomad4 ASJ exome AF: 0.495

Gnomad4 EAS exome AF: 0.106

Gnomad4 SAS exome AF: 0.301

Gnomad4 FIN exome AF: 0.292

Gnomad4 NFE exome AF: 0.403

Gnomad4 OTH exome AF: 0.375

GnomAD4 genome AF: 0.303 AC: 46091 AN: 151960 Hom.: 8438 Cov.: 32 AF XY: 0.299 AC XY: 22207 AN XY: 74252

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.401

Gnomad4 ASJ AF: 0.489

Gnomad4 EAS AF: 0.100

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.401

Gnomad4 OTH AF: 0.344

Alfa AF: 0.395 Hom.: 11856

Bravo AF: 0.307

Asia WGS AF: 0.219 AC: 760 AN: 3478

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

GeneDx

Aug 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.56
DANN	Benign	0.51

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: rs327518; hg19: chr7-127251792; COSMIC: COSV58388384; COSMIC: COSV58388384;