rs534474388
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The ENST00000433033.4(HNF1A-AS1):n.153+1136A>G variant causes a intron change. The variant allele was found at a frequency of 0.0000324 in 493,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000038 ( 0 hom. )
Consequence
HNF1A-AS1
ENST00000433033.4 intron
ENST00000433033.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 5.70
Publications
1 publications found
Genes affected
HNF1A-AS1 (HGNC:26785): (HNF1A antisense RNA 1)
HNF1A (HGNC:11621): (HNF1 homeobox A) The protein encoded by this gene is a transcription factor required for the expression of several liver-specific genes. The encoded protein functions as a homodimer and binds to the inverted palindrome 5'-GTTAATNATTAAC-3'. Defects in this gene are a cause of maturity onset diabetes of the young type 3 (MODY3) and also can result in the appearance of hepatic adenomas. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]
HNF1A Gene-Disease associations (from GenCC):
- monogenic diabetesInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- type 1 diabetes mellitus 20Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Genomics England PanelApp
- diabetes mellitus, noninsulin-dependentInheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
- maturity-onset diabetes of the young type 3Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
- hyperinsulinism due to HNF1A deficiencyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- maturity-onset diabetes of the youngInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- nonpapillary renal cell carcinomaInheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.3).
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| HNF1A | NM_000545.8 | c.-291T>C | upstream_gene_variant | ENST00000257555.11 | NP_000536.6 | |||
| HNF1A | NM_001306179.2 | c.-291T>C | upstream_gene_variant | NP_001293108.2 | ||||
| HNF1A | NM_001406915.1 | c.-291T>C | upstream_gene_variant | NP_001393844.1 | ||||
| HNF1A | XM_024449168.2 | c.-291T>C | upstream_gene_variant | XP_024304936.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| HNF1A | ENST00000257555.11 | c.-291T>C | upstream_gene_variant | 1 | NM_000545.8 | ENSP00000257555.5 |
Frequencies
GnomAD3 genomes 0.0000197 AC: 3AN: 152148Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
3
AN:
152148
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.0000381 AC: 13AN: 341330Hom.: 0 AF XY: 0.0000167 AC XY: 3AN XY: 180020 show subpopulations
GnomAD4 exome
AF:
AC:
13
AN:
341330
Hom.:
AF XY:
AC XY:
3
AN XY:
180020
show subpopulations
African (AFR)
AF:
AC:
0
AN:
10616
American (AMR)
AF:
AC:
0
AN:
15366
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
11048
East Asian (EAS)
AF:
AC:
0
AN:
22140
South Asian (SAS)
AF:
AC:
0
AN:
44788
European-Finnish (FIN)
AF:
AC:
0
AN:
15408
Middle Eastern (MID)
AF:
AC:
0
AN:
1488
European-Non Finnish (NFE)
AF:
AC:
12
AN:
200562
Other (OTH)
AF:
AC:
1
AN:
19914
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.552
Heterozygous variant carriers
0
1
2
4
5
6
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.0000197 AC: 3AN: 152266Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74442 show subpopulations
GnomAD4 genome
AF:
AC:
3
AN:
152266
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74442
show subpopulations
African (AFR)
AF:
AC:
1
AN:
41568
American (AMR)
AF:
AC:
0
AN:
15296
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3466
East Asian (EAS)
AF:
AC:
0
AN:
5172
South Asian (SAS)
AF:
AC:
0
AN:
4824
European-Finnish (FIN)
AF:
AC:
0
AN:
10614
Middle Eastern (MID)
AF:
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
AC:
2
AN:
68006
Other (OTH)
AF:
AC:
0
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.492
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Apr 23, 2018
Genetic Services Laboratory, University of Chicago
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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