13-27921056-G-T

Variant names:

• chr13-27921056-G-T
• rs4430606
• NM_000209.4:c.406+512G>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000209.4(PDX1):​c.406+512G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,136 control chromosomes in the GnomAD database, including 4,006 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (4006 hom., cov: 33)
• Consequence: PDX1 NM_000209.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.510

Genes affected

PDX1 (HGNC:6107): (pancreatic and duodenal homeobox 1) The protein encoded by this gene is a transcriptional activator of several genes, including insulin, somatostatin, glucokinase, islet amyloid polypeptide, and glucose transporter type 2. The encoded nuclear protein is involved in the early development of the pancreas and plays a major role in glucose-dependent regulation of insulin gene expression. Defects in this gene are a cause of pancreatic agenesis, which can lead to early-onset insulin-dependent diabetes mellitus (IDDM), as well as maturity onset diabetes of the young type 4 (MODY4). [provided by RefSeq, Aug 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDX1	NM_000209.4	c.406+512G>T		intron_variant	Intron 1 of 1	ENST00000381033.5	NP_000200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDX1	ENST00000381033.5	c.406+512G>T		intron_variant	Intron 1 of 1	1	NM_000209.4	ENSP00000370421.4

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32758 AN: 152018 Hom.: 4007 Cov.: 33

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.241

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.215 AC: 32750 AN: 152136 Hom.: 4006 Cov.: 33 AF XY: 0.221 AC XY: 16409 AN XY: 74368

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.330

Gnomad4 ASJ AF: 0.312

Gnomad4 EAS AF: 0.443

Gnomad4 SAS AF: 0.167

Gnomad4 FIN AF: 0.251

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.240

Alfa AF: 0.164 Hom.: 484

Bravo AF: 0.221

Asia WGS AF: 0.264 AC: 917 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.5
DANN	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4430606; hg19: chr13-28495193;