chr16-88715442-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001142864.4(PIEZO1):​c.*163G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 935,476 control chromosomes in the GnomAD database, including 8,056 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 910 hom., cov: 33)
Exomes 𝑓: 0.12 ( 7146 hom. )

Consequence

PIEZO1
NM_001142864.4 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.30
Variant links:
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]
CTU2 (HGNC:28005): (cytosolic thiouridylase subunit 2) This gene encodes a protein which is involved in the post-transcriptional modification of transfer RNAs (tRNAs). The encoded protein plays a role in thiolation of uridine residue present at the wobble position in a subset of tRNAs, resulting in enhanced codon reading accuracy. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BP6
Variant 16-88715442-C-T is Benign according to our data. Variant chr16-88715442-C-T is described in ClinVar as [Benign]. Clinvar id is 1246797.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PIEZO1NM_001142864.4 linkuse as main transcriptc.*163G>A 3_prime_UTR_variant 51/51 ENST00000301015.14
CTU2NM_001012759.3 linkuse as main transcript downstream_gene_variant ENST00000453996.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PIEZO1ENST00000301015.14 linkuse as main transcriptc.*163G>A 3_prime_UTR_variant 51/511 NM_001142864.4 P1
CTU2ENST00000453996.7 linkuse as main transcript downstream_gene_variant 1 NM_001012759.3 P2Q2VPK5-1

Frequencies

GnomAD3 genomes
AF:
0.0999
AC:
15198
AN:
152122
Hom.:
908
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0655
Gnomad AMI
AF:
0.0835
Gnomad AMR
AF:
0.0453
Gnomad ASJ
AF:
0.0954
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.0246
Gnomad FIN
AF:
0.146
Gnomad MID
AF:
0.0127
Gnomad NFE
AF:
0.140
Gnomad OTH
AF:
0.0755
GnomAD4 exome
AF:
0.125
AC:
97563
AN:
783240
Hom.:
7146
Cov.:
10
AF XY:
0.121
AC XY:
48084
AN XY:
398194
show subpopulations
Gnomad4 AFR exome
AF:
0.0638
Gnomad4 AMR exome
AF:
0.0405
Gnomad4 ASJ exome
AF:
0.0953
Gnomad4 EAS exome
AF:
0.000213
Gnomad4 SAS exome
AF:
0.0306
Gnomad4 FIN exome
AF:
0.160
Gnomad4 NFE exome
AF:
0.148
Gnomad4 OTH exome
AF:
0.103
GnomAD4 genome
AF:
0.0999
AC:
15208
AN:
152236
Hom.:
910
Cov.:
33
AF XY:
0.0966
AC XY:
7192
AN XY:
74436
show subpopulations
Gnomad4 AFR
AF:
0.0657
Gnomad4 AMR
AF:
0.0452
Gnomad4 ASJ
AF:
0.0954
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.0247
Gnomad4 FIN
AF:
0.146
Gnomad4 NFE
AF:
0.141
Gnomad4 OTH
AF:
0.0742
Alfa
AF:
0.125
Hom.:
195
Bravo
AF:
0.0914
Asia WGS
AF:
0.0220
AC:
76
AN:
3478

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 submitterclinical testingGeneDxJul 09, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.71
CADD
Benign
12
DANN
Benign
0.91

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1061238; hg19: chr16-88781850; API