Variant chr2-232456931-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001631.5(ALPI):c.333C>T(p.Ser111=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0874 in 1,613,426 control chromosomes in the GnomAD database, including 6,464 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.094 ( 717 hom., cov: 32)

Exomes 𝑓: 0.087 ( 5747 hom. )

Consequence

ALPI
NM_001631.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.02

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 2-232456931-C-T is Benign according to our data. Variant chr2-232456931-C-T is described in ClinVar as [Benign]. Clinvar id is 3055586.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-3.02 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALPI	NM_001631.5 linkuse as main transcript	c.333C>T	p.Ser111=	synonymous_variant	4/11	ENST00000295463.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALPI	ENST00000295463.4 linkuse as main transcript	c.333C>T	p.Ser111=	synonymous_variant	4/11	1	NM_001631.5	P1
ALPI	ENST00000457560.1 linkuse as main transcript	c.*262C>T		3_prime_UTR_variant, NMD_transcript_variant	3/10	5

Frequencies

GnomAD3 genomes

AF:

0.0942

AC:

14320

AN:

152094

Hom.:

719

Cov.:

show subpopulations

Gnomad AFR

AF:

0.112

Gnomad AMI

AF:

0.0780

Gnomad AMR

AF:

0.0828

Gnomad ASJ

AF:

0.0927

Gnomad EAS

AF:

0.0834

Gnomad SAS

AF:

0.102

Gnomad FIN

AF:

0.103

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0848

Gnomad OTH

AF:

0.0966

GnomAD3 exomes

AF:

0.0892

AC:

22348

AN:

250516

Hom.:

1114

AF XY:

0.0897

AC XY:

12155

AN XY:

135576

show subpopulations

Gnomad AFR exome

AF:

0.115

Gnomad AMR exome

AF:

0.0632

Gnomad ASJ exome

AF:

0.0856

Gnomad EAS exome

AF:

0.0962

Gnomad SAS exome

AF:

0.106

Gnomad FIN exome

AF:

0.101

Gnomad NFE exome

AF:

0.0858

Gnomad OTH exome

AF:

0.0890

GnomAD4 exome

AF:

0.0867

AC:

126664

AN:

1461214

Hom.:

5747

Cov.:

AF XY:

0.0870

AC XY:

63256

AN XY:

726920

show subpopulations

Gnomad4 AFR exome

AF:

0.113

Gnomad4 AMR exome

AF:

0.0658

Gnomad4 ASJ exome

AF:

0.0892

Gnomad4 EAS exome

AF:

0.0819

Gnomad4 SAS exome

AF:

0.104

Gnomad4 FIN exome

AF:

0.0967

Gnomad4 NFE exome

AF:

0.0845

Gnomad4 OTH exome

AF:

0.0927

GnomAD4 genome

AF:

0.0941

AC:

14318

AN:

152212

Hom.:

717

Cov.:

AF XY:

0.0942

AC XY:

7008

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.112

Gnomad4 AMR

AF:

0.0826

Gnomad4 ASJ

AF:

0.0927

Gnomad4 EAS

AF:

0.0834

Gnomad4 SAS

AF:

0.102

Gnomad4 FIN

AF:

0.103

Gnomad4 NFE

AF:

0.0848

Gnomad4 OTH

AF:

0.0951

Alfa

AF:

0.0874

Hom.:

289

Bravo

AF:

0.0927

Asia WGS

AF:

0.0860

AC:

298

AN:

3478

EpiCase

AF:

0.0925

EpiControl

AF:

0.0919

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ALPI-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 20, 2019

This variant is classified as 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

-0.70

CADD

Benign

7.4

DANN

Benign

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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