rs3824809

chr10-124497138-C-T

Variant summary

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

The NM_022126.4(LHPP):c.531+114C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.701 in 822,090 control chromosomes in the GnomAD database, including 204,404 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 0.72 (40298 hom., cov: 32)
  • Exomes 𝑓: 0.70 (164106 hom.)
• Consequence: LHPP NM_022126.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.257

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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LHPP	NM_022126.4	c.531+114C>T		intron_variant		ENST00000368842.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LHPP	ENST00000368842.10	c.531+114C>T		intron_variant		1	NM_022126.4	P1
LHPP	ENST00000368839.1	c.531+114C>T		intron_variant		1
LHPP	ENST00000392757.8	c.531+114C>T		intron_variant		3
LHPP	ENST00000481452.1	n.177+114C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.725 AC: 110148 AN: 151926 Hom.: 40274 Cov.: 32

Gnomad AFR AF: 0.789

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.771

Gnomad EAS AF: 0.600

Gnomad SAS AF: 0.814

Gnomad FIN AF: 0.792

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.721

GnomAD4 exome AF: 0.696 AC: 466306 AN: 670044 Hom.: 164106 AF XY: 0.701 AC XY: 245730 AN XY: 350442

Gnomad4 AFR exome AF: 0.776

Gnomad4 AMR exome AF: 0.673

Gnomad4 ASJ exome AF: 0.754

Gnomad4 EAS exome AF: 0.619

Gnomad4 SAS exome AF: 0.803

Gnomad4 FIN exome AF: 0.781

Gnomad4 NFE exome AF: 0.675

Gnomad4 OTH exome AF: 0.704

GnomAD4 genome AF: 0.725 AC: 110227 AN: 152046 Hom.: 40298 Cov.: 32 AF XY: 0.728 AC XY: 54100 AN XY: 74314

Gnomad4 AFR AF: 0.789

Gnomad4 AMR AF: 0.676

Gnomad4 ASJ AF: 0.771

Gnomad4 EAS AF: 0.601

Gnomad4 SAS AF: 0.813

Gnomad4 FIN AF: 0.792

Gnomad4 NFE AF: 0.690

Gnomad4 OTH AF: 0.717

Alfa AF: 0.710 Hom.: 19779

Bravo AF: 0.715

Asia WGS AF: 0.735 AC: 2554 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	1.5
Dann	Benign	0.43

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: rs3824809; hg19: chr10-126185707; COSMIC: COSV64330278; COSMIC: COSV64330278;