7-127610586-C-CACAT

Position:

• chr7-127610586-C-CACAT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001366110.1(PAX4):​c.*477_*478insATGT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 401,558 control chromosomes in the GnomAD database, including 28,303 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.40 (8243 hom., cov: 32)
  • Exomes 𝑓: 0.35 (20060 hom.)
• Consequence: PAX4 NM_001366110.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 7-127610586-C-CACAT is Benign according to our data. Variant chr7-127610586-C-CACAT is described in ClinVar as [Benign]. Clinvar id is 358785.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAX4	NM_001366110.1	c.*477_*478insATGT		3_prime_UTR_variant	12/12	ENST00000639438.3	NP_001353039.1
PAX4	NM_001366111.1	c.*265_*266insATGT		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.*477_*478insATGT		3_prime_UTR_variant	12/12	5	NM_001366110.1	ENSP00000491782	A2
PAX4	ENST00000341640.6	c.*477_*478insATGT		3_prime_UTR_variant	9/9	1		ENSP00000339906

Frequencies

GnomAD3 genomes AF: 0.396 AC: 45478 AN: 114758 Hom.: 8234 Cov.: 32

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.562

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.420

GnomAD4 exome AF: 0.351 AC: 100666 AN: 286736 Hom.: 20060 Cov.: 0 AF XY: 0.348 AC XY: 52775 AN XY: 151438

Gnomad4 AFR exome AF: 0.109

Gnomad4 AMR exome AF: 0.425

Gnomad4 ASJ exome AF: 0.496

Gnomad4 EAS exome AF: 0.0985

Gnomad4 SAS exome AF: 0.301

Gnomad4 FIN exome AF: 0.287

Gnomad4 NFE exome AF: 0.396

Gnomad4 OTH exome AF: 0.363

GnomAD4 genome AF: 0.396 AC: 45499 AN: 114822 Hom.: 8243 Cov.: 32 AF XY: 0.390 AC XY: 21927 AN XY: 56162

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.472

Gnomad4 ASJ AF: 0.582

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.381

Gnomad4 NFE AF: 0.478

Gnomad4 OTH AF: 0.423

Alfa AF: 0.0834 Hom.: 213

Asia WGS AF: 0.221 AC: 762 AN: 3460

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs200757052; hg19: chr7-127250640;