20-44401297-GGGAGGGC-G
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The ENST00000316099.10(HNF4A):c.-66_-60del variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.00101 in 1,608,084 control chromosomes in the GnomAD database, including 8 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0014 ( 1 hom., cov: 31)
Exomes 𝑓: 0.00097 ( 7 hom. )
Consequence
HNF4A
ENST00000316099.10 5_prime_UTR
ENST00000316099.10 5_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.96
Genes affected
HNF4A (HGNC:5024): (hepatocyte nuclear factor 4 alpha) The protein encoded by this gene is a nuclear transcription factor which binds DNA as a homodimer. The encoded protein controls the expression of several genes, including hepatocyte nuclear factor 1 alpha, a transcription factor which regulates the expression of several hepatic genes. This gene may play a role in development of the liver, kidney, and intestines. Mutations in this gene have been associated with monogenic autosomal dominant non-insulin-dependent diabetes mellitus type I. Alternative splicing of this gene results in multiple transcript variants encoding several different isoforms. [provided by RefSeq, Apr 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
?
Variant 20-44401297-GGGAGGGC-G is Benign according to our data. Variant chr20-44401297-GGGAGGGC-G is described in ClinVar as [Likely_benign]. Clinvar id is 1302796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00144 (219/152298) while in subpopulation NFE AF= 0.000809 (55/68026). AF 95% confidence interval is 0.000638. There are 1 homozygotes in gnomad4. There are 154 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High AC in GnomAd at 219 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HNF4A | NM_175914.5 | c.50-4751_50-4745del | intron_variant | ENST00000316673.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HNF4A | ENST00000316673.9 | c.50-4751_50-4745del | intron_variant | 1 | NM_175914.5 |
Frequencies
GnomAD3 genomes ? AF: 0.00144 AC: 219AN: 152178Hom.: 1 Cov.: 31
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GnomAD4 exome AF: 0.000966 AC: 1406AN: 1455786Hom.: 7 AF XY: 0.000981 AC XY: 710AN XY: 723994
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 16, 2021 | This variant is associated with the following publications: (PMID: 30663027, 27535533, 10768098) - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 04, 2024 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 06, 2020 | The c.-178_-172delAGGGCGG variant in HNF4A is classified as likely benign because it has been identified in 1.6% (55/3472) of Finnish and in 0.3%(45/15410) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). ACMG/AMP criteria applied: BS1. - |
HNF4A-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 19, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at