rs201167179
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The ENST00000257555.11(HNF1A):c.1623+23C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000657 in 1,613,834 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00070 ( 1 hom. )
Consequence
HNF1A
ENST00000257555.11 intron
ENST00000257555.11 intron
Scores
3
13
Clinical Significance
Conservation
PhyloP100: -0.201
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 -10 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.046997637).
BP6
Variant 12-120999412-C-T is Benign according to our data. Variant chr12-120999412-C-T is described in ClinVar as [Benign]. Clinvar id is 135504.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 40 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HNF1A | NM_000545.8 | c.1623+23C>T | intron_variant | ENST00000257555.11 | NP_000536.6 | |||
HNF1A | XM_024449168.2 | c.1646C>T | p.Pro549Leu | missense_variant | 8/9 | XP_024304936.1 | ||
HNF1A | NM_001306179.2 | c.1623+23C>T | intron_variant | NP_001293108.2 | ||||
HNF1A | NM_001406915.1 | c.1431+23C>T | intron_variant | NP_001393844.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HNF1A | ENST00000257555.11 | c.1623+23C>T | intron_variant | 1 | NM_000545.8 | ENSP00000257555 | P4 |
Frequencies
GnomAD3 genomes AF: 0.000263 AC: 40AN: 152238Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000394 AC: 99AN: 250964Hom.: 0 AF XY: 0.000435 AC XY: 59AN XY: 135782
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GnomAD4 exome AF: 0.000698 AC: 1020AN: 1461478Hom.: 1 Cov.: 57 AF XY: 0.000667 AC XY: 485AN XY: 727036
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GnomAD4 genome AF: 0.000263 AC: 40AN: 152356Hom.: 0 Cov.: 33 AF XY: 0.000268 AC XY: 20AN XY: 74500
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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 rs201167179 with MODY3. - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
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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
Uncertain
D
Vest4
MVP
ClinPred
T
GERP RS
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