rs11245316

Variant names:

• chr10-124609616-T-G
• rs11245316
• NM_022126.4:c.717-3648T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022126.4(LHPP):​c.717-3648T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 152,160 control chromosomes in the GnomAD database, including 4,571 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 0.24 (4571 hom., cov: 33)
• Consequence: LHPP NM_022126.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0260
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LHPP	NM_022126.4	c.717-3648T>G		intron_variant	Intron 6 of 6	ENST00000368842.10	NP_071409.3
LHPP	NM_001167880.2	c.625-3648T>G		intron_variant	Intron 5 of 5		NP_001161352.1
LHPP	NM_001318331.2	c.468-3648T>G		intron_variant	Intron 3 of 3		NP_001305260.1
LHPP	XM_005270026.4	c.832-3648T>G		intron_variant	Intron 7 of 7		XP_005270083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LHPP	ENST00000368842.10	c.717-3648T>G		intron_variant	Intron 6 of 6	1	NM_022126.4	ENSP00000357835.5

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36437 AN: 152042 Hom.: 4568 Cov.: 33

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.0956

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.240 AC: 36474 AN: 152160 Hom.: 4571 Cov.: 33 AF XY: 0.237 AC XY: 17663 AN XY: 74388

African (AFR) AF: 0.229 AC: 9488 AN: 41502

American (AMR) AF: 0.259 AC: 3959 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 660 AN: 3472

East Asian (EAS) AF: 0.260 AC: 1342 AN: 5170

South Asian (SAS) AF: 0.232 AC: 1117 AN: 4824

European-Finnish (FIN) AF: 0.202 AC: 2142 AN: 10612

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.252 AC: 17130 AN: 67976

Other (OTH) AF: 0.232 AC: 490 AN: 2114

Alfa AF: 0.249 Hom.: 11080

Bravo AF: 0.241

Asia WGS AF: 0.243 AC: 844 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.4
DANN	Benign	0.76
PhyloP100		0.026
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs11245316; hg19: chr10-126298185;