rs617182

chr17-49229912-G-A

Variant summary

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

The NM_178500.4(PHOSPHO1):c.-68+556C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 151,958 control chromosomes in the GnomAD database, including 22,900 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 0.53 (22900 hom., cov: 31)
• Consequence: PHOSPHO1 NM_178500.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.163

Genes affected

PHOSPHO1 (HGNC:16815): (phosphoethanolamine/phosphocholine phosphatase 1) Enables pyrophosphatase activity. Predicted to be involved in bone mineralization involved in bone maturation. Predicted to act upstream of or within endochondral ossification. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHOSPHO1	NM_178500.4	c.-68+556C>T		intron_variant		ENST00000310544.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHOSPHO1	ENST00000310544.9	c.-68+556C>T		intron_variant		2	NM_178500.4	P1

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80957 AN: 151840 Hom.: 22870 Cov.: 31

Gnomad AFR AF: 0.722

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.500

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.533 AC: 81029 AN: 151958 Hom.: 22900 Cov.: 31 AF XY: 0.533 AC XY: 39584 AN XY: 74252

Gnomad4 AFR AF: 0.722

Gnomad4 AMR AF: 0.492

Gnomad4 ASJ AF: 0.487

Gnomad4 EAS AF: 0.367

Gnomad4 SAS AF: 0.673

Gnomad4 FIN AF: 0.454

Gnomad4 NFE AF: 0.446

Gnomad4 OTH AF: 0.499

Alfa AF: 0.465 Hom.: 32267

Bravo AF: 0.539

Asia WGS AF: 0.545 AC: 1894 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	5.0
Dann	Benign	0.53

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: rs617182; hg19: chr17-47307274;