7-127610543-G-A

Position:

• chr7-127610543-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001366110.1(PAX4):​c.*521C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 228,788 control chromosomes in the GnomAD database, including 62,305 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.74 (42461 hom., cov: 33)
  • Exomes 𝑓: 0.69 (19844 hom.)
• Consequence: PAX4 NM_001366110.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.00200

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 7-127610543-G-A is Benign according to our data. Variant chr7-127610543-G-A is described in ClinVar as [Benign]. Clinvar id is 358778.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAX4	NM_001366110.1	c.*521C>T		3_prime_UTR_variant	12/12	ENST00000639438.3	NP_001353039.1
PAX4	NM_001366111.1	c.*309C>T		3_prime_UTR_variant	10/10		NP_001353040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAX4	ENST00000639438.3	c.*521C>T		3_prime_UTR_variant	12/12	5	NM_001366110.1	ENSP00000491782	A2
PAX4	ENST00000341640.6	c.*521C>T		3_prime_UTR_variant	9/9	1		ENSP00000339906

Frequencies

GnomAD3 genomes AF: 0.744 AC: 112871 AN: 151774 Hom.: 42435 Cov.: 33

Gnomad AFR AF: 0.716

Gnomad AMI AF: 0.797

Gnomad AMR AF: 0.750

Gnomad ASJ AF: 0.884

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.783

Gnomad OTH AF: 0.745

GnomAD4 exome AF: 0.690 AC: 53072 AN: 76894 Hom.: 19844 Cov.: 0 AF XY: 0.690 AC XY: 27730 AN XY: 40170

Gnomad4 AFR exome AF: 0.661

Gnomad4 AMR exome AF: 0.721

Gnomad4 ASJ exome AF: 0.850

Gnomad4 EAS exome AF: 0.256

Gnomad4 SAS exome AF: 0.683

Gnomad4 FIN exome AF: 0.678

Gnomad4 NFE exome AF: 0.748

Gnomad4 OTH exome AF: 0.722

GnomAD4 genome AF: 0.744 AC: 112947 AN: 151894 Hom.: 42461 Cov.: 33 AF XY: 0.738 AC XY: 54758 AN XY: 74244

Gnomad4 AFR AF: 0.716

Gnomad4 AMR AF: 0.750

Gnomad4 ASJ AF: 0.884

Gnomad4 EAS AF: 0.368

Gnomad4 SAS AF: 0.741

Gnomad4 FIN AF: 0.718

Gnomad4 NFE AF: 0.783

Gnomad4 OTH AF: 0.743

Alfa AF: 0.771 Hom.: 13380

Bravo AF: 0.742

Asia WGS AF: 0.582 AC: 2026 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Maturity onset diabetes mellitus in young Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.47

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: rs712699; hg19: chr7-127250597;