rs164637
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BS1BS2
The NM_007284.4(TWF2):c.411C>T(p.His137=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0436 in 1,614,020 control chromosomes in the GnomAD database, including 1,792 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 0.035 ( 138 hom., cov: 33)
Exomes 𝑓: 0.044 ( 1654 hom. )
Consequence
TWF2
NM_007284.4 synonymous
NM_007284.4 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.310
Genes affected
TWF2 (HGNC:9621): (twinfilin actin binding protein 2) The protein encoded by this gene was identified by its interaction with the catalytic domain of protein kinase C-zeta. The encoded protein contains an actin-binding site and an ATP-binding site. It is most closely related to twinfilin (PTK9), a conserved actin monomer-binding protein. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP7
?
Synonymous conserved (PhyloP=0.31 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0351 (5336/152208) while in subpopulation NFE AF= 0.0492 (3345/67982). AF 95% confidence interval is 0.0478. There are 138 homozygotes in gnomad4. There are 2471 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High AC in GnomAd at 5335 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TWF2 | NM_007284.4 | c.411C>T | p.His137= | synonymous_variant | 5/9 | ENST00000305533.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TWF2 | ENST00000305533.10 | c.411C>T | p.His137= | synonymous_variant | 5/9 | 1 | NM_007284.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0351 AC: 5335AN: 152090Hom.: 136 Cov.: 33
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GnomAD3 exomes AF: 0.0369 AC: 9271AN: 251404Hom.: 224 AF XY: 0.0373 AC XY: 5065AN XY: 135876
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GnomAD4 exome AF: 0.0445 AC: 65035AN: 1461812Hom.: 1654 Cov.: 33 AF XY: 0.0441 AC XY: 32106AN XY: 727222
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GnomAD4 genome ? AF: 0.0351 AC: 5336AN: 152208Hom.: 138 Cov.: 33 AF XY: 0.0332 AC XY: 2471AN XY: 74410
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ClinVar
Not reported inComputational scores
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Name
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BayesDel_noAF
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