Variant rs2242420 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.*388C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 288,568 control chromosomes in the GnomAD database, including 1,923 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1056 hom., cov: 33)

Exomes 𝑓: 0.099 ( 867 hom. )

Consequence

ALPL
NM_000478.6 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.869

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:

ALPL (HGNC:):

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=-0.77).

BP6

Variant 1-21578036-C-T is Benign according to our data. Variant chr1-21578036-C-T is described in ClinVar as [Benign]. Clinvar id is 295566.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.181 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.*388C>T		3_prime_UTR_variant	12/12	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.*388C>T		3_prime_UTR_variant	12/12	1	NM_000478.6	ENSP00000363973.3		P05186-1

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17575

AN:

152140

Hom.:

1056

Cov.:

show subpopulations

Gnomad AFR

AF:

0.102

Gnomad AMI

AF:

0.133

Gnomad AMR

AF:

0.117

Gnomad ASJ

AF:

0.184

Gnomad EAS

AF:

0.191

Gnomad SAS

AF:

0.0689

Gnomad FIN

AF:

0.113

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.116

Gnomad OTH

AF:

0.140

GnomAD4 exome

AF:

0.0989

AC:

13478

AN:

136308

Hom.:

867

Cov.:

AF XY:

0.0967

AC XY:

6843

AN XY:

70790

show subpopulations

Gnomad4 AFR exome

AF:

0.0959

Gnomad4 AMR exome

AF:

0.105

Gnomad4 ASJ exome

AF:

0.154

Gnomad4 EAS exome

AF:

0.167

Gnomad4 SAS exome

AF:

0.0582

Gnomad4 FIN exome

AF:

0.0978

Gnomad4 NFE exome

AF:

0.0972

Gnomad4 OTH exome

AF:

0.108

GnomAD4 genome

AF:

0.115

AC:

17577

AN:

152260

Hom.:

1056

Cov.:

AF XY:

0.115

AC XY:

8553

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.102

Gnomad4 AMR

AF:

0.117

Gnomad4 ASJ

AF:

0.184

Gnomad4 EAS

AF:

0.191

Gnomad4 SAS

AF:

0.0689

Gnomad4 FIN

AF:

0.113

Gnomad4 NFE

AF:

0.116

Gnomad4 OTH

AF:

0.138

Alfa

AF:

0.122

Hom.:

1576

Bravo

AF:

0.119

Asia WGS

AF:

0.107

AC:

372

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Hypophosphatasia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

2.7

DANN

Benign

0.77

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