chr16-88716268-A-G

Variant names:

• chr16-88716268-A-G
• rs2290902
• NM_001142864.4:c.7059T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.343
• Publications: 29 publications found

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]

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]

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142864.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIEZO1	NM_001142864.4	MANE Select	c.7059T>C	p.Pro2353Pro	synonymous	Exon 49 of 51	NP_001136336.2
	MIR4722	NR_039873.1		n.*10T>C		downstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIEZO1	ENST00000301015.14	TSL:1 MANE Select	c.7059T>C	p.Pro2353Pro	synonymous	Exon 49 of 51	ENSP00000301015.9
	PIEZO1	ENST00000419505.5	TSL:1	n.*637T>C		non_coding_transcript_exon	Exon 8 of 10	ENSP00000406358.1
	PIEZO1	ENST00000419505.5	TSL:1	n.*637T>C		3_prime_UTR	Exon 8 of 10	ENSP00000406358.1

Frequencies

GnomAD3 genomes AF: 0.880 AC: 133868 AN: 152152 Hom.: 58996 Cov.: 34

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

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.: 55 AF XY: 0.893 AC XY: 583357 AN XY: 652920

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

GnomAD4 genome AF: 0.880 AC: 133952 AN: 152270 Hom.: 59024 Cov.: 34 AF XY: 0.876 AC XY: 65239 AN XY: 74438

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

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

Submissions by phenotype

not provided Benign:4

Jul 05, 2018

GeneDx

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

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.4
DANN	Benign	0.36
PhyloP100		-0.34
PromoterAI		-0.021	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2290902; hg19: chr16-88782676; COSMIC: COSV56339331; COSMIC: COSV56339331;