Genetic Variant ALPI:c.-7C>G (chr2-232456193-C-G) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

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 (no stars).

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 no assertion criteria provided B:1

Conservation

PhyloP100: 1.21

Publications

1 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 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 VariationId is 3042489.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001631.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALPI	NM_001631.5	MANE Select	c.-7C>G		5_prime_UTR	Exon 1 of 11	NP_001622.2	P09923

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ALPI	ENST00000295463.4	TSL:1 MANE Select	c.-7C>G	5_prime_UTR	Exon 1 of 11	ENSP00000295463.3	P09923
ALPI	ENST00000457560.1	TSL:5	n.-7C>G	non_coding_transcript_exon	Exon 1 of 10	ENSP00000413068.1	F8WEQ0
ALPI	ENST00000457560.1	TSL:5	n.-7C>G	5_prime_UTR	Exon 1 of 10	ENSP00000413068.1	F8WEQ0

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

GnomAD2 exomes

AF:

0.00251

AC:

628

AN:

250492

AF XY:

0.00265

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 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

African (AFR)

AF:

0.000837

AC:

AN:

33456

American (AMR)

AF:

0.00112

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.000498

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.00225

AC:

194

AN:

86216

European-Finnish (FIN)

AF:

0.00188

AC:

100

AN:

53268

Middle Eastern (MID)

AF:

0.000391

AC:

AN:

5120

European-Non Finnish (NFE)

AF:

0.00454

AC:

5049

AN:

1111954

Other (OTH)

AF:

0.00229

AC:

138

AN:

60320

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

358

717

1075

1434

1792

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

198

396

594

792

990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00255

AC:

389

AN:

152310

Hom.:

Cov.:

AF XY:

0.00232

AC XY:

173

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.00101

AC:

AN:

41566

American (AMR)

AF:

0.00124

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.000865

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00165

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00216

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00426

AC:

290

AN:

68008

Other (OTH)

AF:

0.00189

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

111

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

ALPI-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.9

(source)

DANN

Benign

0.38

PhyloP100

1.2

PromoterAI

0.087

Neutral

(source)

Mutation Taster

=300/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over