chr4-25351693-G-A
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_024936.3(ZCCHC4):c.1011+4G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00136 in 1,601,122 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0068 ( 10 hom., cov: 32)
Exomes 𝑓: 0.00079 ( 15 hom. )
Consequence
ZCCHC4
NM_024936.3 splice_donor_region, intron
NM_024936.3 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.00007813
2
Clinical Significance
Conservation
PhyloP100: -1.02
Genes affected
ZCCHC4 (HGNC:22917): (zinc finger CCHC-type containing 4) Enables S-adenosyl-L-methionine binding activity; rRNA (adenine-N6-)-methyltransferase activity; and zinc ion binding activity. Involved in positive regulation of translation and rRNA methylation. Located in cytoplasm and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]
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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=-0.81).
BP6
?
Variant 4-25351693-G-A is Benign according to our data. Variant chr4-25351693-G-A is described in ClinVar as [Benign]. Clinvar id is 720331.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00677 (1031/152214) while in subpopulation AFR AF= 0.0233 (967/41536). AF 95% confidence interval is 0.0221. There are 10 homozygotes in gnomad4. There are 484 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 10 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZCCHC4 | NM_024936.3 | c.1011+4G>A | splice_donor_region_variant, intron_variant | ENST00000302874.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZCCHC4 | ENST00000302874.9 | c.1011+4G>A | splice_donor_region_variant, intron_variant | 1 | NM_024936.3 | P1 | |||
ZCCHC4 | ENST00000507760.5 | c.687-10166G>A | intron_variant, NMD_transcript_variant | 1 | |||||
ZCCHC4 | ENST00000505451.5 | n.1036+4G>A | splice_donor_region_variant, intron_variant, non_coding_transcript_variant | 1 | |||||
ZCCHC4 | ENST00000505412.1 | c.604+4G>A | splice_donor_region_variant, intron_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00673 AC: 1023AN: 152096Hom.: 10 Cov.: 32
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GnomAD3 exomes AF: 0.00184 AC: 452AN: 246182Hom.: 7 AF XY: 0.00135 AC XY: 180AN XY: 133476
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GnomAD4 exome AF: 0.000787 AC: 1141AN: 1448908Hom.: 15 Cov.: 28 AF XY: 0.000700 AC XY: 505AN XY: 721258
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GnomAD4 genome ? AF: 0.00677 AC: 1031AN: 152214Hom.: 10 Cov.: 32 AF XY: 0.00650 AC XY: 484AN XY: 74418
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at