rs10518048
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2
The NM_006885.4(ZFHX3):c.3216+3628C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0257 in 152,306 control chromosomes in the GnomAD database, including 79 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.026 ( 79 hom., cov: 32)
Consequence
ZFHX3
NM_006885.4 intron
NM_006885.4 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.369
Genes affected
ZFHX3 (HGNC:777): (zinc finger homeobox 3) This gene encodes a transcription factor with multiple homeodomains and zinc finger motifs, and regulates myogenic and neuronal differentiation. The encoded protein suppresses expression of the alpha-fetoprotein gene by binding to an AT-rich enhancer motif. The protein has also been shown to negatively regulate c-Myb, and transactivate the cell cycle inhibitor cyclin-dependent kinase inhibitor 1A (also known as p21CIP1). This gene is reported to function as a tumor suppressor in several cancers, and sequence variants of this gene are also associated with atrial fibrillation. Multiple transcript variants expressed from alternate promoters and encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0257 (3918/152306) while in subpopulation AFR AF= 0.0364 (1514/41568). AF 95% confidence interval is 0.0349. There are 79 homozygotes in gnomad4. There are 1867 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 3918 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZFHX3 | NM_006885.4 | c.3216+3628C>T | intron_variant | ENST00000268489.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZFHX3 | ENST00000268489.10 | c.3216+3628C>T | intron_variant | 1 | NM_006885.4 | P1 | |||
ZFHX3 | ENST00000397992.5 | c.474+3628C>T | intron_variant | 1 | |||||
ZFHX3 | ENST00000641206.2 | c.3216+3628C>T | intron_variant | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0257 AC: 3915AN: 152188Hom.: 78 Cov.: 32
GnomAD3 genomes
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32
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? AF: 0.0257 AC: 3918AN: 152306Hom.: 79 Cov.: 32 AF XY: 0.0251 AC XY: 1867AN XY: 74474
GnomAD4 genome
?
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32
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1867
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74474
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33
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3478
ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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