16-88715641-C-T
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001142864.4(PIEZO1):c.7530G>A(p.Pro2510=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00152 in 1,550,234 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0075 ( 11 hom., cov: 33)
Exomes 𝑓: 0.00087 ( 19 hom. )
Consequence
PIEZO1
NM_001142864.4 synonymous
NM_001142864.4 synonymous
Scores
1
12
Clinical Significance
Conservation
PhyloP100: -4.68
Genes affected
PIEZO1 (HGNC:28993): (piezo type mechanosensitive ion channel component 1 (Er blood group)) The protein encoded by this gene is a mechanically-activated ion channel that links mechanical forces to biological signals. The encoded protein contains 36 transmembrane domains and functions as a homotetramer. Defects in this gene have been associated with dehydrated hereditary stomatocytosis. [provided by RefSeq, Jul 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0023759902).
BP6
?
Variant 16-88715641-C-T is Benign according to our data. Variant chr16-88715641-C-T is described in ClinVar as [Benign]. Clinvar id is 789647.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-88715641-C-T is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-4.68 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00745 (1135/152328) while in subpopulation AFR AF= 0.0251 (1042/41574). AF 95% confidence interval is 0.0238. There are 11 homozygotes in gnomad4. There are 562 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd at 1132 AD,BG gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIEZO1 | NM_001142864.4 | c.7530G>A | p.Pro2510= | synonymous_variant | 51/51 | ENST00000301015.14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIEZO1 | ENST00000301015.14 | c.7530G>A | p.Pro2510= | synonymous_variant | 51/51 | 1 | NM_001142864.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00744 AC: 1132AN: 152210Hom.: 11 Cov.: 33
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.00175 AC: 270AN: 154470Hom.: 2 AF XY: 0.00134 AC XY: 110AN XY: 82116
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GnomAD4 exome AF: 0.000874 AC: 1222AN: 1397906Hom.: 19 Cov.: 32 AF XY: 0.000719 AC XY: 496AN XY: 689454
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GnomAD4 genome ? AF: 0.00745 AC: 1135AN: 152328Hom.: 11 Cov.: 33 AF XY: 0.00754 AC XY: 562AN XY: 74490
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Asia WGS
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 22, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 13, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
D;N
PROVEAN
Benign
N
REVEL
Benign
Sift
Pathogenic
D
Polyphen
B
Vest4
MutPred
Loss of relative solvent accessibility (P = 0.0404);
MVP
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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