Variant 7-127611031-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001366110.1(PAX4):c.*33A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0151 in 1,580,706 control chromosomes in the GnomAD database, including 222 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 8 hom., cov: 33)

Exomes 𝑓: 0.016 ( 214 hom. )

Consequence

PAX4
NM_001366110.1 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.178

Variant links:

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]

PAX4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 7-127611031-T-G is Benign according to our data. Variant chr7-127611031-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 358794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0106 (1612/152262) while in subpopulation NFE AF= 0.0166 (1130/68002). AF 95% confidence interval is 0.0158. There are 8 homozygotes in gnomad4. There are 797 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1612 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAX4	NM_001366110.1 linkuse as main transcript	c.*33A>C		3_prime_UTR_variant	12/12	ENST00000639438.3
PAX4	NM_001366111.1 linkuse as main transcript	c.914-46A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAX4	ENST00000639438.3 linkuse as main transcript	c.*33A>C		3_prime_UTR_variant	12/12	5	NM_001366110.1	A2

Frequencies

GnomAD3 genomes

AF:

0.0106

AC:

1612

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00328

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00281

Gnomad ASJ

AF:

0.00866

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.0238

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0166

Gnomad OTH

AF:

0.00623

GnomAD3 exomes

AF:

0.0103

AC:

2074

AN:

202238

Hom.:

AF XY:

0.0102

AC XY:

1102

AN XY:

108354

show subpopulations

Gnomad AFR exome

AF:

0.00215

Gnomad AMR exome

AF:

0.00155

Gnomad ASJ exome

AF:

0.00522

Gnomad EAS exome

AF:

0.0000640

Gnomad SAS exome

AF:

0.00275

Gnomad FIN exome

AF:

0.0217

Gnomad NFE exome

AF:

0.0169

Gnomad OTH exome

AF:

0.00888

GnomAD4 exome

AF:

0.0156

AC:

22323

AN:

1428444

Hom.:

214

Cov.:

AF XY:

0.0153

AC XY:

10806

AN XY:

707494

show subpopulations

Gnomad4 AFR exome

AF:

0.00226

Gnomad4 AMR exome

AF:

0.00176

Gnomad4 ASJ exome

AF:

0.00633

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00305

Gnomad4 FIN exome

AF:

0.0234

Gnomad4 NFE exome

AF:

0.0182

Gnomad4 OTH exome

AF:

0.0110

GnomAD4 genome

AF:

0.0106

AC:

1612

AN:

152262

Hom.:

Cov.:

AF XY:

0.0107

AC XY:

797

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00327

Gnomad4 AMR

AF:

0.00274

Gnomad4 ASJ

AF:

0.00866

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.0238

Gnomad4 NFE

AF:

0.0166

Gnomad4 OTH

AF:

0.00617

Alfa

AF:

0.0114

Hom.:

Bravo

AF:

0.00862

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 09, 2018	- -

Maturity onset diabetes mellitus in young

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.3

DANN

Benign

0.57

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over