Variant 7-127610572-C-T 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.*492G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0164 in 275,170 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 29 hom., cov: 31)

Exomes 𝑓: 0.010 ( 17 hom. )

Consequence

PAX4
NM_001366110.1 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.29

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=-0.96).

BP6

Variant 7-127610572-C-T is Benign according to our data. Variant chr7-127610572-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 358784.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0328 (2493/76080) while in subpopulation SAS AF= 0.0527 (127/2410). AF 95% confidence interval is 0.0479. There are 29 homozygotes in gnomad4. There are 1172 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2493 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAX4	NM_001366110.1 linkuse as main transcript	c.*492G>A		3_prime_UTR_variant	12/12	ENST00000639438.3
PAX4	NM_001366111.1 linkuse as main transcript	c.*280G>A		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAX4	ENST00000639438.3 linkuse as main transcript	c.*492G>A		3_prime_UTR_variant	12/12	5	NM_001366110.1	A2
PAX4	ENST00000341640.6 linkuse as main transcript	c.*492G>A		3_prime_UTR_variant	9/9	1			O43316-4

Frequencies

GnomAD3 genomes

AF:

0.0327

AC:

2487

AN:

76024

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0505

Gnomad AMI

AF:

0.0864

Gnomad AMR

AF:

0.0204

Gnomad ASJ

AF:

0.0169

Gnomad EAS

AF:

0.00520

Gnomad SAS

AF:

0.0532

Gnomad FIN

AF:

0.0221

Gnomad MID

AF:

0.0462

Gnomad NFE

AF:

0.0304

Gnomad OTH

AF:

0.0288

GnomAD4 exome

AF:

0.0101

AC:

2012

AN:

199090

Hom.:

Cov.:

AF XY:

0.0106

AC XY:

1123

AN XY:

105922

show subpopulations

Gnomad4 AFR exome

AF:

0.0172

Gnomad4 AMR exome

AF:

0.00482

Gnomad4 ASJ exome

AF:

0.00682

Gnomad4 EAS exome

AF:

0.00214

Gnomad4 SAS exome

AF:

0.0164

Gnomad4 FIN exome

AF:

0.00795

Gnomad4 NFE exome

AF:

0.00990

Gnomad4 OTH exome

AF:

0.00917

GnomAD4 genome

AF:

0.0328

AC:

2493

AN:

76080

Hom.:

Cov.:

AF XY:

0.0316

AC XY:

1172

AN XY:

37136

show subpopulations

Gnomad4 AFR

AF:

0.0507

Gnomad4 AMR

AF:

0.0204

Gnomad4 ASJ

AF:

0.0169

Gnomad4 EAS

AF:

0.00521

Gnomad4 SAS

AF:

0.0527

Gnomad4 FIN

AF:

0.0221

Gnomad4 NFE

AF:

0.0304

Gnomad4 OTH

AF:

0.0303

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

-0.96

CADD

Benign

0.39

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

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