chr17-49225076-C-G

Variant names:

• chr17-49225076-C-G
• rs766758664
• ENST00000514112.1:c.49G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_178500.4(PHOSPHO1):​c.46-72G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PHOSPHO1 NM_178500.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.24
• Publications: 1 publications found

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]

FLJ40194 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.035702527).
• BP6: Variant 17-49225076-C-G is Benign according to our data. Variant chr17-49225076-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3417908.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHOSPHO1	NM_178500.4	c.46-72G>C		intron_variant	Intron 2 of 2	ENST00000310544.9	NP_848595.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHOSPHO1	ENST00000310544.9	c.46-72G>C		intron_variant	Intron 2 of 2	2	NM_178500.4	ENSP00000311925.4
PHOSPHO1	ENST00000574638.1	c.46-72G>C		intron_variant	Intron 2 of 2	3		ENSP00000461392.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152222 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1292418 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 627928

African (AFR) AF: 0.00 AC: 0 AN: 28320

American (AMR) AF: 0.00 AC: 0 AN: 20022

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18958

East Asian (EAS) AF: 0.00 AC: 0 AN: 35012

South Asian (SAS) AF: 0.00 AC: 0 AN: 63522

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31002

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5042

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1036734

Other (OTH) AF: 0.00 AC: 0 AN: 53806

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152222 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74364

African (AFR) AF: 0.0000241 AC: 1 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Nov 08, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	17
DANN	Benign	0.70
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.47	T;.;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.036	T;T;T;T
MetaSVM	Benign	-1.1	T
PhyloP100		1.2
PROVEAN	Benign	0.0	N;N;N;N
REVEL	Benign	0.050
Sift	Benign	0.90	T;T;T;T
Sift4G	Benign	0.79	T;T;.;.
Vest4		0.16
MutPred		0.15		Gain of methylation at G17 (P = 0.046);Gain of methylation at G17 (P = 0.046);Gain of methylation at G17 (P = 0.046);.;
MVP		0.043
ClinPred		0.045	T
GERP RS		2.1
gMVP		0.25

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: rs766758664; hg19: chr17-47302438;