chr4-109912889-G-A
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_001963.6(EGF):c.-447G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000776 in 179,086 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.00081 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00056 ( 0 hom. )
Consequence
EGF
NM_001963.6 5_prime_UTR
NM_001963.6 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.31
Genes affected
EGF (HGNC:3229): (epidermal growth factor) This gene encodes a member of the epidermal growth factor superfamily. The encoded preproprotein is proteolytically processed to generate the 53-amino acid epidermal growth factor peptide. This protein acts a potent mitogenic factor that plays an important role in the growth, proliferation and differentiation of numerous cell types. This protein acts by binding with high affinity to the cell surface receptor, epidermal growth factor receptor. Defects in this gene are the cause of hypomagnesemia type 4. Dysregulation of this gene has been associated with the growth and progression of certain cancers. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. [provided by RefSeq, Jan 2016]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
Variant 4-109912889-G-A is Benign according to our data. Variant chr4-109912889-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 347218.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EGF | NM_001963.6 | c.-447G>A | 5_prime_UTR_variant | 1/24 | ENST00000265171.10 | ||
EGF | NM_001178130.3 | c.-447G>A | 5_prime_UTR_variant | 1/23 | |||
EGF | NM_001178131.3 | c.-447G>A | 5_prime_UTR_variant | 1/23 | |||
EGF | NM_001357021.2 | c.-447G>A | 5_prime_UTR_variant | 1/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EGF | ENST00000265171.10 | c.-447G>A | 5_prime_UTR_variant | 1/24 | 1 | NM_001963.6 | P1 | ||
EGF | ENST00000509793.5 | c.-447G>A | 5_prime_UTR_variant | 1/23 | 2 | ||||
EGF | ENST00000652245.1 | c.-447G>A | 5_prime_UTR_variant | 1/20 |
Frequencies
GnomAD3 genomes AF: 0.000821 AC: 125AN: 152202Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.000560 AC: 15AN: 26766Hom.: 0 Cov.: 0 AF XY: 0.000444 AC XY: 6AN XY: 13510
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GnomAD4 genome AF: 0.000814 AC: 124AN: 152320Hom.: 0 Cov.: 33 AF XY: 0.000846 AC XY: 63AN XY: 74482
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Renal hypomagnesemia 4 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at