7-127610587-G-A

Position:

• chr7-127610587-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.*477C>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 0.338 in 442,146 control chromosomes in the GnomAD database, including 29,530 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (8254 hom., cov: 32)
  • Exomes 𝑓: 0.36 (21276 hom.)
• Consequence: PAX4 NM_001366110.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.601

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=-0.95).
• BP6: Variant 7-127610587-G-A is Benign according to our data. Variant chr7-127610587-G-A is described in ClinVar as [Benign]. Clinvar id is 358787.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAX4	NM_001366110.1	c.*477C>T		3_prime_UTR_variant	12/12	ENST00000639438.3	NP_001353039.1
PAX4	NM_001366111.1	c.*265C>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.*477C>T		3_prime_UTR_variant	12/12	5	NM_001366110.1	ENSP00000491782	A2
PAX4	ENST00000341640.6	c.*477C>T		3_prime_UTR_variant	9/9	1		ENSP00000339906

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45507 AN: 151752 Hom.: 8245 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.327

GnomAD4 exome AF: 0.357 AC: 103713 AN: 290276 Hom.: 21276 Cov.: 0 AF XY: 0.355 AC XY: 54434 AN XY: 153414

Gnomad4 AFR exome AF: 0.110

Gnomad4 AMR exome AF: 0.431

Gnomad4 ASJ exome AF: 0.496

Gnomad4 EAS exome AF: 0.109

Gnomad4 SAS exome AF: 0.303

Gnomad4 FIN exome AF: 0.297

Gnomad4 NFE exome AF: 0.400

Gnomad4 OTH exome AF: 0.366

GnomAD4 genome AF: 0.300 AC: 45528 AN: 151870 Hom.: 8254 Cov.: 32 AF XY: 0.296 AC XY: 21945 AN XY: 74212

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.396

Gnomad4 ASJ AF: 0.487

Gnomad4 EAS AF: 0.101

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.294

Gnomad4 NFE AF: 0.397

Gnomad4 OTH AF: 0.331

Alfa AF: 0.547 Hom.: 5074

Bravo AF: 0.302

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	-0.95
CADD	Benign	0.46
DANN	Benign	0.49

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: rs327520; hg19: chr7-127250641;