dbSNP rs3740540: LHPP:c.717-7666G>A (chr10-124605598-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_022126.4(LHPP):c.717-7666G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,312 control chromosomes in the GnomAD database, including 4,294 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 0.22 ( 4288 hom., cov: 32)

Exomes 𝑓: 0.29 ( 6 hom. )

Consequence

LHPP
NM_022126.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.363

Publications

17 publications found

Variant links:

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]

LHPP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
LHPP	NM_022126.4 link	c.717-7666G>A	intron_variant	Intron 6 of 6	ENST00000368842.10	NP_071409.3	Q9H008-1
LHPP	NM_001167880.2 link	c.625-7666G>A	intron_variant	Intron 5 of 5		NP_001161352.1	Q9H008-2
LHPP	NM_001318331.2 link	c.468-7666G>A	intron_variant	Intron 3 of 3		NP_001305260.1	Q9H008
LHPP	XM_005270026.4 link	c.832-7666G>A	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 link	c.717-7666G>A		intron_variant	Intron 6 of 6	1	NM_022126.4	ENSP00000357835.5		Q9H008-1

Frequencies

GnomAD3 genomes

AF:

0.220

AC:

33421

AN:

152032

Hom.:

4285

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0894

Gnomad AMI

AF:

0.258

Gnomad AMR

AF:

0.250

Gnomad ASJ

AF:

0.331

Gnomad EAS

AF:

0.189

Gnomad SAS

AF:

0.249

Gnomad FIN

AF:

0.316

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.271

Gnomad OTH

AF:

0.229

GnomAD4 exome

AF:

0.290

AC:

AN:

162

Hom.:

AF XY:

0.275

AC XY:

AN XY:

120

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.100

AC:

AN:

European-Finnish (FIN)

AF:

0.417

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.283

AC:

AN:

106

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.531

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.220

AC:

33436

AN:

152150

Hom.:

4288

Cov.:

AF XY:

0.222

AC XY:

16480

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.0894

AC:

3710

AN:

41512

American (AMR)

AF:

0.250

AC:

3824

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.331

AC:

1150

AN:

3470

East Asian (EAS)

AF:

0.188

AC:

973

AN:

5164

South Asian (SAS)

AF:

0.250

AC:

1201

AN:

4808

European-Finnish (FIN)

AF:

0.316

AC:

3352

AN:

10596

Middle Eastern (MID)

AF:

0.262

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.271

AC:

18428

AN:

67998

Other (OTH)

AF:

0.230

AC:

486

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1290

2581

3871

5162

6452

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

352

704

1056

1408

1760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.256

Hom.:

20868

Bravo

AF:

0.211

Asia WGS

AF:

0.262

AC:

910

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

5.1

(source)

DANN

Benign

0.82

PhyloP100

-0.36

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over