Variant 16-88715442-C-T details in Genebe, Genetics Data Aggregator

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

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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]

PIEZO1 links:

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]

CTU2 links:

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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
PIEZO1	NM_001142864.4 linkuse as main transcript	c.*163G>A		3_prime_UTR_variant	51/51	ENST00000301015.14
CTU2	NM_001012759.3 linkuse as main transcript			downstream_gene_variant		ENST00000453996.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIEZO1	ENST00000301015.14 linkuse as main transcript	c.*163G>A		3_prime_UTR_variant	51/51	1	NM_001142864.4	P1
CTU2	ENST00000453996.7 linkuse as main transcript			downstream_gene_variant		1	NM_001012759.3	P2	Q2VPK5-1

Frequencies

GnomAD3 genomes

AF:

0.0999

AC:

15198

AN:

152122

Hom.:

908

Cov.:

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.:

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.:

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:

AN:

3478

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

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.

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