7-127610777-G-A

Position:

• chr7-127610777-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.*287C>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 0.00539 in 1,188,094 control chromosomes in the GnomAD database, including 445 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0057 (67 hom., cov: 34)
  • Exomes 𝑓: 0.0054 (378 hom.)
• Consequence: PAX4 NM_001366110.1 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.179

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=-0.82).
• BP6: Variant 7-127610777-G-A is Benign according to our data. Variant chr7-127610777-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 358790.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAX4	NM_001366110.1	c.*287C>T		3_prime_UTR_variant	12/12	ENST00000639438.3
PAX4	NM_001366111.1	c.*75C>T		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAX4	ENST00000639438.3	c.*287C>T		3_prime_UTR_variant	12/12	5	NM_001366110.1	A2
PAX4	ENST00000341640.6	c.*287C>T		3_prime_UTR_variant	9/9	1
PAX4	ENST00000378740.6			downstream_gene_variant		1		P2

Frequencies

GnomAD3 genomes AF: 0.00569 AC: 866 AN: 152200 Hom.: 67 Cov.: 34

Gnomad AFR AF: 0.000845

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00479

GnomAD4 exome AF: 0.00535 AC: 5544 AN: 1035776 Hom.: 378 Cov.: 13 AF XY: 0.00519 AC XY: 2715 AN XY: 523146

Gnomad4 AFR exome AF: 0.000562

Gnomad4 AMR exome AF: 0.000346

Gnomad4 ASJ exome AF: 0.000542

Gnomad4 EAS exome AF: 0.145

Gnomad4 SAS exome AF: 0.00109

Gnomad4 FIN exome AF: 0.00142

Gnomad4 NFE exome AF: 0.000116

Gnomad4 OTH exome AF: 0.00721

GnomAD4 genome AF: 0.00567 AC: 864 AN: 152318 Hom.: 67 Cov.: 34 AF XY: 0.00660 AC XY: 492 AN XY: 74492

Gnomad4 AFR AF: 0.000842

Gnomad4 AMR AF: 0.000458

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.00290

Gnomad4 FIN AF: 0.000565

Gnomad4 NFE AF: 0.000250

Gnomad4 OTH AF: 0.00474

Alfa AF: 0.00226 Hom.: 4

Bravo AF: 0.00609

Asia WGS AF: 0.0390 AC: 136 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Maturity onset diabetes mellitus in young Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Likely 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	-0.82
CADD	Benign	2.4
DANN	Benign	0.58

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: rs12669223; hg19: chr7-127250831;