rs2290902

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001142864.4(PIEZO1):c.7059T>C(p.Pro2353Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.892 in 1,491,590 control chromosomes in the GnomAD database, including 593,652 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.88 ( 59024 hom., cov: 34)

Exomes 𝑓: 0.89 ( 534628 hom. )

Consequence

PIEZO1
NM_001142864.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.343

Publications

29 publications found

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:

MIR4722 (HGNC:41782): (microRNA 4722) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR4722 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 16-88716268-A-G is Benign according to our data. Variant chr16-88716268-A-G is described in ClinVar as Benign. ClinVar VariationId is 440040.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.343 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIEZO1	NM_001142864.4 link	c.7059T>C	p.Pro2353Pro	synonymous_variant	Exon 49 of 51	ENST00000301015.14	NP_001136336.2	Q92508
MIR4722	NR_039873.1 link	n.*10T>C		downstream_gene_variant
MIR4722	unassigned_transcript_2911	n.*10T>C		downstream_gene_variant
MIR4722	unassigned_transcript_2912	n.*47T>C		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIEZO1	ENST00000301015.14 link	c.7059T>C	p.Pro2353Pro	synonymous_variant	Exon 49 of 51	1	NM_001142864.4	ENSP00000301015.9		Q92508

Frequencies

GnomAD3 genomes

AF:

0.880

AC:

133868

AN:

152152

Hom.:

58996

Cov.:

show subpopulations

Gnomad AFR

AF:

0.840

Gnomad AMI

AF:

0.944

Gnomad AMR

AF:

0.873

Gnomad ASJ

AF:

0.950

Gnomad EAS

AF:

0.895

Gnomad SAS

AF:

0.864

Gnomad FIN

AF:

0.852

Gnomad MID

AF:

0.956

Gnomad NFE

AF:

0.904

Gnomad OTH

AF:

0.889

GnomAD2 exomes

AF:

0.883

AC:

97080

AN:

109958

AF XY:

0.883

show subpopulations

Gnomad AFR exome

AF:

0.836

Gnomad AMR exome

AF:

0.862

Gnomad ASJ exome

AF:

0.951

Gnomad EAS exome

AF:

0.882

Gnomad FIN exome

AF:

0.864

Gnomad NFE exome

AF:

0.907

Gnomad OTH exome

AF:

0.904

GnomAD4 exome

AF:

0.893

AC:

1196461

AN:

1339320

Hom.:

534628

Cov.:

AF XY:

0.893

AC XY:

583357

AN XY:

652920

show subpopulations

African (AFR)

AF:

0.839

AC:

25295

AN:

30156

American (AMR)

AF:

0.860

AC:

25455

AN:

29584

Ashkenazi Jewish (ASJ)

AF:

0.949

AC:

19937

AN:

21004

East Asian (EAS)

AF:

0.892

AC:

31367

AN:

35182

South Asian (SAS)

AF:

0.863

AC:

59914

AN:

69418

European-Finnish (FIN)

AF:

0.871

AC:

39718

AN:

45584

Middle Eastern (MID)

AF:

0.934

AC:

5029

AN:

5382

European-Non Finnish (NFE)

AF:

0.898

AC:

940482

AN:

1047654

Other (OTH)

AF:

0.890

AC:

49264

AN:

55356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

7177

14355

21532

28710

35887

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20964

41928

62892

83856

104820

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.880

AC:

133952

AN:

152270

Hom.:

59024

Cov.:

AF XY:

0.876

AC XY:

65239

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.840

AC:

34906

AN:

41546

American (AMR)

AF:

0.874

AC:

13365

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.950

AC:

3298

AN:

3472

East Asian (EAS)

AF:

0.894

AC:

4629

AN:

5176

South Asian (SAS)

AF:

0.864

AC:

4174

AN:

4830

European-Finnish (FIN)

AF:

0.852

AC:

9051

AN:

10618

Middle Eastern (MID)

AF:

0.956

AC:

281

AN:

294

European-Non Finnish (NFE)

AF:

0.904

AC:

61511

AN:

68010

Other (OTH)

AF:

0.888

AC:

1876

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

846

1692

2538

3384

4230

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

900

1800

2700

3600

4500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.898

Hom.:

52692

Bravo

AF:

0.878

Asia WGS

AF:

0.864

AC:

3005

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Jul 05, 2018

GeneDx

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

- -

Nov 29, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Lymphatic malformation 6

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

2.4

(source)

DANN

Benign

0.36

PhyloP100

-0.34

PromoterAI

-0.021

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over