rs532689884
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2
The ENST00000544413.2(HNF1A):c.1624-8G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000558 in 1,613,672 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 Benign (★).
Frequency
Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000055 ( 0 hom. )
Consequence
HNF1A
ENST00000544413.2 splice_region, splice_polypyrimidine_tract, intron
ENST00000544413.2 splice_region, splice_polypyrimidine_tract, intron
Scores
2
14
Clinical Significance
Conservation
PhyloP100: 0.229
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 Likely_benign. Variant got -6 ACMG points.
BP6
?
Variant 12-120999454-G-A is Benign according to our data. Variant chr12-120999454-G-A is described in ClinVar as [Benign]. Clinvar id is 135507.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAd4 at 9 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HNF1A | NM_000545.8 | c.1624-29G>A | intron_variant | ENST00000257555.11 | |||
HNF1A | XM_024449168.2 | c.1688G>A | p.Arg563Gln | missense_variant | 8/9 | ||
HNF1A | NM_001306179.2 | c.1624-8G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
HNF1A | NM_001406915.1 | c.1432-29G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HNF1A | ENST00000257555.11 | c.1624-29G>A | intron_variant | 1 | NM_000545.8 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000592 AC: 9AN: 152076Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000718 AC: 18AN: 250632Hom.: 0 AF XY: 0.0000885 AC XY: 12AN XY: 135668
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GnomAD4 exome AF: 0.0000554 AC: 81AN: 1461478Hom.: 0 Cov.: 69 AF XY: 0.0000578 AC XY: 42AN XY: 727048
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GnomAD4 genome ? AF: 0.0000591 AC: 9AN: 152194Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6AN XY: 74394
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ClinVar
Significance: Benign
Submissions summary: Benign:1Other:1
Revision: criteria provided, single submitter
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 rs532689884 with MODY3. - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Uncertain
D
MutationTaster
Benign
N;N;N;N
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Vest4
MVP
ClinPred
T
GERP RS
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at