Variant rs2275376 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000478.6(ALPL):c.862+51G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,578,162 control chromosomes in the GnomAD database, including 21,470 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 3142 hom., cov: 33)

Exomes 𝑓: 0.14 ( 18328 hom. )

Consequence

ALPL
NM_000478.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.34

Variant links:

Genes affected

ALPL (HGNC:438): (alkaline phosphatase, biomineralization associated) This gene encodes a member of the alkaline phosphatase family of proteins. There are at least four distinct but related alkaline phosphatases: intestinal, placental, placental-like, and liver/bone/kidney (tissue non-specific). The first three are located together on chromosome 2, while the tissue non-specific form is located on chromosome 1. The product of this gene is a membrane bound glycosylated enzyme that is not expressed in any particular tissue and is, therefore, referred to as the tissue-nonspecific form of the enzyme. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature enzyme. This enzyme may play a role in bone mineralization. Mutations in this gene have been linked to hypophosphatasia, a disorder that is characterized by hypercalcemia and skeletal defects. [provided by RefSeq, Oct 2015]

ALPL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 1-21570425-G-A is Benign according to our data. Variant chr1-21570425-G-A is described in ClinVar as [Benign]. Clinvar id is 1177589.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-21570425-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALPL	NM_000478.6 linkuse as main transcript	c.862+51G>A		intron_variant		ENST00000374840.8	NP_000469.3	P05186-1A0A024RAB4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALPL	ENST00000374840.8 linkuse as main transcript	c.862+51G>A		intron_variant		1	NM_000478.6	ENSP00000363973.3		P05186-1

Frequencies

GnomAD3 genomes

AF:

0.184

AC:

27964

AN:

151924

Hom.:

3128

Cov.:

show subpopulations

Gnomad AFR

AF:

0.255

Gnomad AMI

AF:

0.118

Gnomad AMR

AF:

0.225

Gnomad ASJ

AF:

0.140

Gnomad EAS

AF:

0.451

Gnomad SAS

AF:

0.234

Gnomad FIN

AF:

0.188

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.111

Gnomad OTH

AF:

0.178

GnomAD3 exomes

AF:

0.183

AC:

44585

AN:

244254

Hom.:

5093

AF XY:

0.177

AC XY:

23454

AN XY:

132244

show subpopulations

Gnomad AFR exome

AF:

0.260

Gnomad AMR exome

AF:

0.249

Gnomad ASJ exome

AF:

0.137

Gnomad EAS exome

AF:

0.439

Gnomad SAS exome

AF:

0.214

Gnomad FIN exome

AF:

0.184

Gnomad NFE exome

AF:

0.107

Gnomad OTH exome

AF:

0.155

GnomAD4 exome

AF:

0.141

AC:

200929

AN:

1426120

Hom.:

18328

Cov.:

AF XY:

0.142

AC XY:

100921

AN XY:

711124

show subpopulations

Gnomad4 AFR exome

AF:

0.269

Gnomad4 AMR exome

AF:

0.245

Gnomad4 ASJ exome

AF:

0.138

Gnomad4 EAS exome

AF:

0.511

Gnomad4 SAS exome

AF:

0.217

Gnomad4 FIN exome

AF:

0.176

Gnomad4 NFE exome

AF:

0.111

Gnomad4 OTH exome

AF:

0.155

GnomAD4 genome

AF:

0.184

AC:

28016

AN:

152042

Hom.:

3142

Cov.:

AF XY:

0.192

AC XY:

14255

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.255

Gnomad4 AMR

AF:

0.225

Gnomad4 ASJ

AF:

0.140

Gnomad4 EAS

AF:

0.453

Gnomad4 SAS

AF:

0.233

Gnomad4 FIN

AF:

0.188

Gnomad4 NFE

AF:

0.111

Gnomad4 OTH

AF:

0.182

Alfa

AF:

0.141

Hom.:

330

Bravo

AF:

0.192

Asia WGS

AF:

0.327

AC:

1137

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 20, 2018	- -

Infantile hypophosphatasia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Adult hypophosphatasia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Childhood hypophosphatasia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.10

DANN

Benign

0.38

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over