Variant chr2-232456193-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001631.5(ALPI):c.-7C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0037 in 1,613,180 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0026 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0038 ( 17 hom. )

Consequence

ALPI
NM_001631.5 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.21

Variant links:

Genes affected

ALPI (HGNC:437): (alkaline phosphatase, intestinal) There are at least four distinct but related alkaline phosphatases: intestinal, placental, placental-like, and liver/bone/kidney (tissue non-specific). The intestinal alkaline phosphatase gene encodes a digestive brush-border enzyme. This enzyme is a component of the gut mucosal defense system and is thought to function in the detoxification of lipopolysaccharide, and in the prevention of bacterial translocation in the gut. [provided by RefSeq, Dec 2014]

ALPI links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 2-232456193-C-G is Benign according to our data. Variant chr2-232456193-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3042489.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALPI	NM_001631.5 linkuse as main transcript	c.-7C>G		5_prime_UTR_variant	1/11	ENST00000295463.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALPI	ENST00000295463.4 linkuse as main transcript	c.-7C>G		5_prime_UTR_variant	1/11	1	NM_001631.5	P1
ALPI	ENST00000457560.1 linkuse as main transcript	c.-7C>G		5_prime_UTR_variant, NMD_transcript_variant	1/10	5

Frequencies

GnomAD3 genomes

AF:

0.00256

AC:

389

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00165

Gnomad FIN

AF:

0.00216

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00426

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00251

AC:

628

AN:

250492

Hom.:

AF XY:

0.00265

AC XY:

359

AN XY:

135522

show subpopulations

Gnomad AFR exome

AF:

0.000556

Gnomad AMR exome

AF:

0.00113

Gnomad ASJ exome

AF:

0.000499

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00258

Gnomad FIN exome

AF:

0.00213

Gnomad NFE exome

AF:

0.00381

Gnomad OTH exome

AF:

0.00279

GnomAD4 exome

AF:

0.00382

AC:

5574

AN:

1460870

Hom.:

Cov.:

AF XY:

0.00378

AC XY:

2745

AN XY:

726758

show subpopulations

Gnomad4 AFR exome

AF:

0.000837

Gnomad4 AMR exome

AF:

0.00112

Gnomad4 ASJ exome

AF:

0.000498

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00225

Gnomad4 FIN exome

AF:

0.00188

Gnomad4 NFE exome

AF:

0.00454

Gnomad4 OTH exome

AF:

0.00229

GnomAD4 genome

AF:

0.00255

AC:

389

AN:

152310

Hom.:

Cov.:

AF XY:

0.00232

AC XY:

173

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00101

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00165

Gnomad4 FIN

AF:

0.00216

Gnomad4 NFE

AF:

0.00426

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00272

Hom.:

Bravo

AF:

0.00237

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00442

EpiControl

AF:

0.00344

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ALPI-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.9

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