Variant rs2275375 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+58C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 1,561,994 control chromosomes in the GnomAD database, including 45,066 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5493 hom., cov: 33)

Exomes 𝑓: 0.23 ( 39573 hom. )

Consequence

ALPL
NM_000478.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.10

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 1-21570432-C-T is Benign according to our data. Variant chr1-21570432-C-T is described in ClinVar as [Benign]. Clinvar id is 1177590.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-21570432-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALPL	NM_000478.6 linkuse as main transcript	c.862+58C>T		intron_variant		ENST00000374840.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALPL	ENST00000374840.8 linkuse as main transcript	c.862+58C>T		intron_variant		1	NM_000478.6	P1	P05186-1

Frequencies

GnomAD3 genomes

AF:

0.261

AC:

39605

AN:

151840

Hom.:

5477

Cov.:

show subpopulations

Gnomad AFR

AF:

0.306

Gnomad AMI

AF:

0.188

Gnomad AMR

AF:

0.294

Gnomad ASJ

AF:

0.271

Gnomad EAS

AF:

0.477

Gnomad SAS

AF:

0.303

Gnomad FIN

AF:

0.306

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.200

Gnomad OTH

AF:

0.261

GnomAD4 exome

AF:

0.228

AC:

320800

AN:

1410036

Hom.:

39573

AF XY:

0.229

AC XY:

160943

AN XY:

703912

show subpopulations

Gnomad4 AFR exome

AF:

0.321

Gnomad4 AMR exome

AF:

0.293

Gnomad4 ASJ exome

AF:

0.276

Gnomad4 EAS exome

AF:

0.548

Gnomad4 SAS exome

AF:

0.289

Gnomad4 FIN exome

AF:

0.295

Gnomad4 NFE exome

AF:

0.200

Gnomad4 OTH exome

AF:

0.244

GnomAD4 genome

AF:

0.261

AC:

39662

AN:

151958

Hom.:

5493

Cov.:

AF XY:

0.270

AC XY:

20021

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.306

Gnomad4 AMR

AF:

0.294

Gnomad4 ASJ

AF:

0.271

Gnomad4 EAS

AF:

0.480

Gnomad4 SAS

AF:

0.302

Gnomad4 FIN

AF:

0.306

Gnomad4 NFE

AF:

0.200

Gnomad4 OTH

AF:

0.264

Alfa

AF:

0.229

Hom.:

524

Bravo

AF:

0.264

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

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

-0.91

CADD

Benign

0.45

DANN

Benign

0.45

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