rs146021107

Variant names:

• chr13-27920029-AG-A
• rs146021107
• NM_000209.4:c.-106delG

Your query was ambiguous. Multiple possible variants found:

• chr13-27920029-AG-A
• chr13-27920029-AG-AGG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000209.4(PDX1):​c.-106delG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 1,345,708 control chromosomes in the GnomAD database, including 37,586 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4301 hom., cov: 27)
  • Exomes 𝑓: 0.23 (33285 hom.)
• Consequence: PDX1 NM_000209.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.786
• Publications: 6 publications found

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]

PDX1 Gene-Disease associations (from GenCC):

• maturity-onset diabetes of the young type 4

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• pancreatic agenesis 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp
• permanent neonatal diabetes mellitus

  Inheritance: AD, AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
• monogenic diabetes

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• maturity-onset diabetes of the young

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• pancreatic agenesis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 13-27920029-AG-A is Benign according to our data. Variant chr13-27920029-AG-A is described in ClinVar as Benign. ClinVar VariationId is 1179450.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000209.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDX1	NM_000209.4	MANE Select	c.-106delG		5_prime_UTR	Exon 1 of 2	NP_000200.1	P52945

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDX1	ENST00000381033.5	TSL:1 MANE Select	c.-106delG		5_prime_UTR	Exon 1 of 2	ENSP00000370421.4	P52945

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34618 AN: 152062 Hom.: 4297 Cov.: 27

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.248

GnomAD4 exome AF: 0.228 AC: 271783 AN: 1193528 Hom.: 33285 Cov.: 9 AF XY: 0.226 AC XY: 135045 AN XY: 596986

African (AFR) AF: 0.165 AC: 4559 AN: 27568

American (AMR) AF: 0.312 AC: 11004 AN: 35274

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 6930 AN: 23734

East Asian (EAS) AF: 0.471 AC: 16347 AN: 34676

South Asian (SAS) AF: 0.172 AC: 12893 AN: 74748

European-Finnish (FIN) AF: 0.249 AC: 11459 AN: 46014

Middle Eastern (MID) AF: 0.236 AC: 891 AN: 3772

European-Non Finnish (NFE) AF: 0.218 AC: 195294 AN: 896822

Other (OTH) AF: 0.244 AC: 12406 AN: 50920

GnomAD4 genome AF: 0.228 AC: 34631 AN: 152180 Hom.: 4301 Cov.: 27 AF XY: 0.233 AC XY: 17312 AN XY: 74384

African (AFR) AF: 0.168 AC: 6981 AN: 41556

American (AMR) AF: 0.336 AC: 5139 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 1082 AN: 3470

East Asian (EAS) AF: 0.444 AC: 2287 AN: 5152

South Asian (SAS) AF: 0.168 AC: 809 AN: 4826

European-Finnish (FIN) AF: 0.252 AC: 2673 AN: 10598

Middle Eastern (MID) AF: 0.195 AC: 57 AN: 292

European-Non Finnish (NFE) AF: 0.219 AC: 14917 AN: 67970

Other (OTH) AF: 0.247 AC: 520 AN: 2108

Alfa AF: 0.226 Hom.: 493

Bravo AF: 0.234

Asia WGS AF: 0.269 AC: 935 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.79
Mutation Taster		=297/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs146021107; hg19: chr13-28494166;