16-88740930-T-C

Position:

• chr16-88740930-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000301015.14(PIEZO1):​c.465+548A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 152,510 control chromosomes in the GnomAD database, including 18,842 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.49 (18793 hom., cov: 33)
  • Exomes 𝑓: 0.49 (49 hom.)
• Consequence: PIEZO1 ENST00000301015.14 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27

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]

ENSG00000224888 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIEZO1	NM_001142864.4	c.465+548A>G		intron_variant		ENST00000301015.14	NP_001136336.2
HSALR1	NR_103774.1	n.3281T>C		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIEZO1	ENST00000301015.14	c.465+548A>G		intron_variant		1	NM_001142864.4	ENSP00000301015.9
ENSG00000224888	ENST00000567968.2	n.4033T>C		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.493 AC: 75001 AN: 152026 Hom.: 18784 Cov.: 33

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.537

GnomAD4 exome AF: 0.495 AC: 181 AN: 366 Hom.: 49 Cov.: 0 AF XY: 0.495 AC XY: 96 AN XY: 194

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.438

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.507

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.493 AC: 75042 AN: 152144 Hom.: 18793 Cov.: 33 AF XY: 0.491 AC XY: 36508 AN XY: 74382

Gnomad4 AFR AF: 0.412

Gnomad4 AMR AF: 0.527

Gnomad4 ASJ AF: 0.575

Gnomad4 EAS AF: 0.395

Gnomad4 SAS AF: 0.575

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.536

Alfa AF: 0.536 Hom.: 34087

Bravo AF: 0.493

Asia WGS AF: 0.501 AC: 1741 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.37
DANN	Benign	0.22
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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

Other links and lift over

dbSNP: rs750740; hg19: chr16-88807338;