16-88715671-G-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001142864.4(PIEZO1):c.7500C>T(p.Tyr2500Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 1,550,144 control chromosomes in the GnomAD database, including 12,615 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1115 hom., cov: 33)

Exomes 𝑓: 0.12 ( 11500 hom. )

Consequence

PIEZO1
NM_001142864.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.213

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]

PIEZO1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0010708272).

BP6

Variant 16-88715671-G-A is Benign according to our data. Variant chr16-88715671-G-A is described in ClinVar as [Benign]. Clinvar id is 381962.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-88715671-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.213 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIEZO1	NM_001142864.4 link	c.7500C>T	p.Tyr2500Tyr	synonymous_variant	Exon 51 of 51	ENST00000301015.14	NP_001136336.2	Q92508

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIEZO1	ENST00000301015.14 link	c.7500C>T	p.Tyr2500Tyr	synonymous_variant	Exon 51 of 51	1	NM_001142864.4	ENSP00000301015.9		Q92508

Frequencies

GnomAD3 genomes

AF:

0.107

AC:

16333

AN:

152154

Hom.:

1117

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0333

Gnomad AMI

AF:

0.276

Gnomad AMR

AF:

0.161

Gnomad ASJ

AF:

0.109

Gnomad EAS

AF:

0.128

Gnomad SAS

AF:

0.0749

Gnomad FIN

AF:

0.140

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.133

Gnomad OTH

AF:

0.125

GnomAD3 exomes

AF:

0.120

AC:

18677

AN:

155468

Hom.:

1222

AF XY:

0.117

AC XY:

9666

AN XY:

82564

show subpopulations

Gnomad AFR exome

AF:

0.0297

Gnomad AMR exome

AF:

0.156

Gnomad ASJ exome

AF:

0.109

Gnomad EAS exome

AF:

0.118

Gnomad SAS exome

AF:

0.0701

Gnomad FIN exome

AF:

0.139

Gnomad NFE exome

AF:

0.132

Gnomad OTH exome

AF:

0.130

GnomAD4 exome

AF:

0.124

AC:

173937

AN:

1397872

Hom.:

11500

Cov.:

AF XY:

0.123

AC XY:

84558

AN XY:

689418

show subpopulations

Gnomad4 AFR exome

AF:

0.0318

Gnomad4 AMR exome

AF:

0.155

Gnomad4 ASJ exome

AF:

0.111

Gnomad4 EAS exome

AF:

0.171

Gnomad4 SAS exome

AF:

0.0721

Gnomad4 FIN exome

AF:

0.141

Gnomad4 NFE exome

AF:

0.128

Gnomad4 OTH exome

AF:

0.123

GnomAD4 genome

AF:

0.107

AC:

16335

AN:

152272

Hom.:

1115

Cov.:

AF XY:

0.109

AC XY:

8097

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0335

Gnomad4 AMR

AF:

0.160

Gnomad4 ASJ

AF:

0.109

Gnomad4 EAS

AF:

0.128

Gnomad4 SAS

AF:

0.0746

Gnomad4 FIN

AF:

0.140

Gnomad4 NFE

AF:

0.133

Gnomad4 OTH

AF:

0.123

Alfa

AF:

0.112

Hom.:

778

Bravo

AF:

0.106

TwinsUK

AF:

0.128

AC:

473

ALSPAC

AF:

0.125

AC:

483

ExAC

AF:

0.0847

AC:

2210

Asia WGS

AF:

0.0990

AC:

344

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 29, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Dec 21, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.17

CADD

Benign

0.25

DANN

Benign

0.90

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.79

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.51

MetaRNN

Benign

0.0011

MetaSVM

Benign

-1.1

PROVEAN

Benign

1.2

REVEL

Benign

0.080

Sift

Pathogenic

0.0

Polyphen

0.0010

Vest4

0.28

ClinPred

0.022

GERP RS

-2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over