chr4-109912994-C-T
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_001963.6(EGF):c.-342C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00668 in 303,384 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.012 ( 29 hom., cov: 32)
Exomes 𝑓: 0.0014 ( 5 hom. )
Consequence
EGF
NM_001963.6 5_prime_UTR
NM_001963.6 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0270
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 Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
Variant 4-109912994-C-T is Benign according to our data. Variant chr4-109912994-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1317925.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.012 (1821/152312) while in subpopulation AFR AF= 0.0413 (1715/41562). AF 95% confidence interval is 0.0396. There are 29 homozygotes in gnomad4. There are 835 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 29 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EGF | NM_001963.6 | c.-342C>T | 5_prime_UTR_variant | 1/24 | ENST00000265171.10 | ||
EGF | NM_001178130.3 | c.-342C>T | 5_prime_UTR_variant | 1/23 | |||
EGF | NM_001178131.3 | c.-342C>T | 5_prime_UTR_variant | 1/23 | |||
EGF | NM_001357021.2 | c.-342C>T | 5_prime_UTR_variant | 1/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EGF | ENST00000265171.10 | c.-342C>T | 5_prime_UTR_variant | 1/24 | 1 | NM_001963.6 | P1 | ||
EGF | ENST00000509793.5 | c.-342C>T | 5_prime_UTR_variant | 1/23 | 2 | ||||
EGF | ENST00000652245.1 | c.-342C>T | 5_prime_UTR_variant | 1/20 |
Frequencies
GnomAD3 genomes AF: 0.0119 AC: 1808AN: 152194Hom.: 29 Cov.: 32
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GnomAD4 exome AF: 0.00137 AC: 207AN: 151072Hom.: 5 Cov.: 0 AF XY: 0.00111 AC XY: 89AN XY: 80476
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GnomAD4 genome AF: 0.0120 AC: 1821AN: 152312Hom.: 29 Cov.: 32 AF XY: 0.0112 AC XY: 835AN XY: 74482
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 14, 2020 | - - |
Computational scores
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Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at