Variant 13-30735647-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_001629.4(ALOX5AP):c.42C>T(p.Ile14=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000942 in 1,614,124 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0045 ( 8 hom., cov: 32)

Exomes 𝑓: 0.00057 ( 9 hom. )

Consequence

ALOX5AP
NM_001629.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.82

Variant links:

Genes affected

ALOX5AP (HGNC:436): (arachidonate 5-lipoxygenase activating protein) This gene encodes a protein which, with 5-lipoxygenase, is required for leukotriene synthesis. Leukotrienes are arachidonic acid metabolites which have been implicated in various types of inflammatory responses, including asthma, arthritis and psoriasis. This protein localizes to the plasma membrane. Inhibitors of its function impede translocation of 5-lipoxygenase from the cytoplasm to the cell membrane and inhibit 5-lipoxygenase activation. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Feb 2011]

ALOX5AP links:

LOC124903146 (HGNC:):

LOC124903146 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 13-30735647-C-T is Benign according to our data. Variant chr13-30735647-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3041525.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-4.82 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000567 (829/1461886) while in subpopulation AFR AF= 0.0167 (560/33480). AF 95% confidence interval is 0.0156. There are 9 homozygotes in gnomad4_exome. There are 384 alleles in male gnomad4_exome subpopulation. Median coverage is 35. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ALOX5AP	NM_001629.4 linkuse as main transcript	c.42C>T	p.Ile14=	synonymous_variant	1/5	ENST00000380490.5
LOC124903146	XR_007063743.1 linkuse as main transcript	n.221-2910G>A		intron_variant, non_coding_transcript_variant
ALOX5AP	NM_001204406.2 linkuse as main transcript	c.213C>T	p.Ile71=	synonymous_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALOX5AP	ENST00000380490.5 linkuse as main transcript	c.42C>T	p.Ile14=	synonymous_variant	1/5	1	NM_001629.4	P1
ALOX5AP	ENST00000617770.4 linkuse as main transcript	c.213C>T	p.Ile71=	synonymous_variant	2/6	1

Frequencies

GnomAD3 genomes

AF:

0.00450

AC:

685

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0156

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00122

AC:

306

AN:

251436

Hom.:

AF XY:

0.000920

AC XY:

125

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.0138

Gnomad AMR exome

AF:

0.000607

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00167

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.000567

AC:

829

AN:

1461886

Hom.:

Cov.:

AF XY:

0.000528

AC XY:

384

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.0167

Gnomad4 AMR exome

AF:

0.000715

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00132

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000198

Gnomad4 OTH exome

AF:

0.00149

GnomAD4 genome

AF:

0.00455

AC:

692

AN:

152238

Hom.:

Cov.:

AF XY:

0.00443

AC XY:

330

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0158

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00229

Hom.:

Bravo

AF:

0.00515

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ALOX5AP-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 04, 2023

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

-0.39

CADD

Benign

4.3

DANN

Benign

0.76

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