2-218429441-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_007127.3(VIL1):c.724G>A(p.Asp242Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 1,613,914 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000099 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00011 ( 0 hom. )
Consequence
VIL1
NM_007127.3 missense
NM_007127.3 missense
Scores
1
8
10
Clinical Significance
Conservation
PhyloP100: 9.83
Genes affected
VIL1 (HGNC:12690): (villin 1) This gene encodes a member of a family of calcium-regulated actin-binding proteins. This protein represents a dominant part of the brush border cytoskeleton which functions in the capping, severing, and bundling of actin filaments. Two mRNAs of 2.7 kb and 3.5 kb have been observed; they result from utilization of alternate poly-adenylation signals present in the terminal exon. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.04573673).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VIL1 | NM_007127.3 | c.724G>A | p.Asp242Asn | missense_variant | 7/20 | ENST00000248444.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VIL1 | ENST00000248444.10 | c.724G>A | p.Asp242Asn | missense_variant | 7/20 | 1 | NM_007127.3 | P1 | |
VIL1 | ENST00000440053.1 | c.724G>A | p.Asp242Asn | missense_variant | 6/9 | 1 | |||
VIL1 | ENST00000392114.6 | c.-183-27G>A | intron_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000985 AC: 15AN: 152230Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000215 AC: 54AN: 250944Hom.: 0 AF XY: 0.000147 AC XY: 20AN XY: 135696
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GnomAD4 exome AF: 0.000105 AC: 154AN: 1461684Hom.: 0 Cov.: 32 AF XY: 0.0000853 AC XY: 62AN XY: 727130
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GnomAD4 genome ? AF: 0.0000985 AC: 15AN: 152230Hom.: 0 Cov.: 33 AF XY: 0.0000941 AC XY: 7AN XY: 74366
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 11, 2021 | The c.724G>A (p.D242N) alteration is located in exon 7 (coding exon 6) of the VIL1 gene. This alteration results from a G to A substitution at nucleotide position 724, causing the aspartic acid (D) at amino acid position 242 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Uncertain
D;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Benign
T;D
Polyphen
D;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
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