rs2244608
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000545.8(HNF1A):c.326+91A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 1,161,610 control chromosomes in the GnomAD database, including 69,227 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.30 ( 7481 hom., cov: 32)
Exomes 𝑓: 0.34 ( 61746 hom. )
Consequence
HNF1A
NM_000545.8 intron
NM_000545.8 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.26
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
?
Variant 12-120979185-A-G is Benign according to our data. Variant chr12-120979185-A-G is described in ClinVar as [Benign]. Clinvar id is 676859.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HNF1A | NM_000545.8 | c.326+91A>G | intron_variant | ENST00000257555.11 | |||
HNF1A | NM_001306179.2 | c.326+91A>G | intron_variant | ||||
HNF1A | NM_001406915.1 | c.326+91A>G | intron_variant | ||||
HNF1A | XM_024449168.2 | c.326+91A>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HNF1A | ENST00000257555.11 | c.326+91A>G | intron_variant | 1 | NM_000545.8 | P4 | |||
HNF1A-AS1 | ENST00000619441.1 | n.128+1459T>C | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.296 AC: 45010AN: 151868Hom.: 7481 Cov.: 32
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GnomAD4 exome AF: 0.343 AC: 346535AN: 1009624Hom.: 61746 AF XY: 0.348 AC XY: 178460AN XY: 513206
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GnomAD4 genome ? AF: 0.296 AC: 45014AN: 151986Hom.: 7481 Cov.: 32 AF XY: 0.306 AC XY: 22699AN XY: 74288
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Maturity onset diabetes mellitus in young Benign:1
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 rs2244608 with MODY3. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 14, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
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