rs2045184

chr10-124526735-C-G

Variant summary

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

The NM_022126.4(LHPP):c.716+9464C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 152,126 control chromosomes in the GnomAD database, including 8,302 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 0.31 (8302 hom., cov: 32)
• Consequence: LHPP NM_022126.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560

Genes affected

LHPP (HGNC:30042): (phospholysine phosphohistidine inorganic pyrophosphate phosphatase) Enables inorganic diphosphatase activity and protein homodimerization activity. Involved in phosphate-containing compound metabolic process. Located in cytosol and nuclear speck. [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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LHPP	NM_022126.4	c.716+9464C>G		intron_variant		ENST00000368842.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LHPP	ENST00000368842.10	c.716+9464C>G		intron_variant		1	NM_022126.4	P1
LHPP	ENST00000368839.1	c.624+28607C>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47824 AN: 152008 Hom.: 8293 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.315 AC: 47847 AN: 152126 Hom.: 8302 Cov.: 32 AF XY: 0.310 AC XY: 23086 AN XY: 74364

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.378

Gnomad4 ASJ AF: 0.340

Gnomad4 EAS AF: 0.348

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.391

Gnomad4 OTH AF: 0.334

Alfa AF: 0.349 Hom.: 1232

Bravo AF: 0.316

Asia WGS AF: 0.271 AC: 944 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.1
Dann	Benign	0.73

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: rs2045184; hg19: chr10-126215304;