rs3824809

Variant names:

• chr10-124497138-C-T
• rs3824809
• NM_022126.4:c.531+114C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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=-0.94).
• 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 rank	MANE	Protein	UniProt
LHPP	NM_022126.4	c.531+114C>T		intron_variant	Intron 4 of 6	ENST00000368842.10	NP_071409.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LHPP	ENST00000368842.10	c.531+114C>T		intron_variant	Intron 4 of 6	1	NM_022126.4	ENSP00000357835.5
LHPP	ENST00000368839.1	c.531+114C>T		intron_variant	Intron 4 of 5	1		ENSP00000357832.1
LHPP	ENST00000392757.8	c.531+114C>T		intron_variant	Intron 4 of 5	3		ENSP00000376512.4
LHPP	ENST00000481452.1	n.177+114C>T		intron_variant	Intron 2 of 3	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

African (AFR) AF: 0.776 AC: 12163 AN: 15680

American (AMR) AF: 0.673 AC: 18118 AN: 26932

Ashkenazi Jewish (ASJ) AF: 0.754 AC: 11837 AN: 15692

East Asian (EAS) AF: 0.619 AC: 20106 AN: 32492

South Asian (SAS) AF: 0.803 AC: 43106 AN: 53712

European-Finnish (FIN) AF: 0.781 AC: 36915 AN: 47284

Middle Eastern (MID) AF: 0.777 AC: 2915 AN: 3754

European-Non Finnish (NFE) AF: 0.675 AC: 298068 AN: 441730

Other (OTH) AF: 0.704 AC: 23078 AN: 32768

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

African (AFR) AF: 0.789 AC: 32730 AN: 41496

American (AMR) AF: 0.676 AC: 10331 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.771 AC: 2674 AN: 3468

East Asian (EAS) AF: 0.601 AC: 3081 AN: 5128

South Asian (SAS) AF: 0.813 AC: 3918 AN: 4820

European-Finnish (FIN) AF: 0.792 AC: 8392 AN: 10596

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.690 AC: 46874 AN: 67934

Other (OTH) AF: 0.717 AC: 1515 AN: 2112

Alfa AF: 0.707 Hom.: 28022

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
PhyloP100		-0.26
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: rs3824809; hg19: chr10-126185707; COSMIC: COSV64330278; COSMIC: COSV64330278;