rs765596650
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_000545.8(HNF1A):c.1502-14T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000122 in 1,613,626 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00013 ( 0 hom. )
Consequence
HNF1A
NM_000545.8 splice_polypyrimidine_tract, intron
NM_000545.8 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0150
Genes affected
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
?
Variant 12-120999254-T-C is Benign according to our data. Variant chr12-120999254-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 256596.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=1}.
BS2
?
High AC in GnomAd at 11 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HNF1A | NM_000545.8 | c.1502-14T>C | splice_polypyrimidine_tract_variant, intron_variant | ENST00000257555.11 | |||
HNF1A | NM_001306179.2 | c.1502-14T>C | splice_polypyrimidine_tract_variant, intron_variant | ||||
HNF1A | NM_001406915.1 | c.1310-14T>C | splice_polypyrimidine_tract_variant, intron_variant | ||||
HNF1A | XM_024449168.2 | c.1502-14T>C | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HNF1A | ENST00000257555.11 | c.1502-14T>C | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000545.8 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000724 AC: 11AN: 151958Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000878 AC: 22AN: 250530Hom.: 0 AF XY: 0.000111 AC XY: 15AN XY: 135674
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GnomAD4 exome AF: 0.000127 AC: 186AN: 1461550Hom.: 0 Cov.: 32 AF XY: 0.000149 AC XY: 108AN XY: 727084
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GnomAD4 genome ? AF: 0.0000723 AC: 11AN: 152076Hom.: 0 Cov.: 33 AF XY: 0.0000941 AC XY: 7AN XY: 74350
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Nov 25, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Maturity onset diabetes mellitus in young Benign:1
Likely benign, criteria provided, single submitter | research | Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic | - | Mutations in HNF1A gene can predispose to MODY3. It is associated with both micro and macrovascular complications of diabetes, especially cardiovascular complications. Associated with glucosuria. May respond well to sulfonylureas. However, more evidence is required to confer the association of this particular variant rs765596650 with MODY3. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 17, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at