13-30744112-C-T

Position:

• chr13-30744112-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_001629.4(ALOX5AP):​c.123C>T​(p.Ser41Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00512 in 1,614,118 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0043 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0052 (34 hom.)
• Consequence: ALOX5AP NM_001629.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.833

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 13-30744112-C-T is Benign according to our data. Variant chr13-30744112-C-T is described in ClinVar as [Benign]. Clinvar id is 773270.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.833 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALOX5AP	NM_001629.4	c.123C>T	p.Ser41Ser	synonymous_variant	2/5	ENST00000380490.5	NP_001620.2
ALOX5AP	NM_001204406.2	c.294C>T	p.Ser98Ser	synonymous_variant	3/6		NP_001191335.1
ALOX5AP	XM_017020522.3	c.-118C>T		5_prime_UTR_variant	1/5		XP_016876011.1
LOC124903146	XR_007063743.1	n.220+397G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALOX5AP	ENST00000380490.5	c.123C>T	p.Ser41Ser	synonymous_variant	2/5	1	NM_001629.4	ENSP00000369858.3
ALOX5AP	ENST00000617770.4	c.294C>T	p.Ser98Ser	synonymous_variant	3/6	1		ENSP00000479870.1
ALOX5AP	ENST00000479597.1	n.263C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.00432 AC: 658 AN: 152218 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00154

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0115

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00517

Gnomad OTH AF: 0.00860

GnomAD3 exomes AF: 0.00469 AC: 1180 AN: 251420 Hom.: 11 AF XY: 0.00460 AC XY: 625 AN XY: 135900

Gnomad AFR exome AF: 0.00111

Gnomad AMR exome AF: 0.00928

Gnomad ASJ exome AF: 0.00665

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00118

Gnomad FIN exome AF: 0.000554

Gnomad NFE exome AF: 0.00597

Gnomad OTH exome AF: 0.00766

GnomAD4 exome AF: 0.00520 AC: 7602 AN: 1461782 Hom.: 34 Cov.: 31 AF XY: 0.00512 AC XY: 3725 AN XY: 727208

Gnomad4 AFR exome AF: 0.00161

Gnomad4 AMR exome AF: 0.00948

Gnomad4 ASJ exome AF: 0.00708

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00104

Gnomad4 FIN exome AF: 0.000955

Gnomad4 NFE exome AF: 0.00572

Gnomad4 OTH exome AF: 0.00580

GnomAD4 genome AF: 0.00432 AC: 658 AN: 152336 Hom.: 2 Cov.: 33 AF XY: 0.00375 AC XY: 279 AN XY: 74494

Gnomad4 AFR AF: 0.00154

Gnomad4 AMR AF: 0.0115

Gnomad4 ASJ AF: 0.0101

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00104

Gnomad4 NFE AF: 0.00517

Gnomad4 OTH AF: 0.00851

Alfa AF: 0.00383 Hom.: 0

Bravo AF: 0.00537

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00693

EpiControl AF: 0.00717

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	13
DANN	Benign	0.91

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs41351946; hg19: chr13-31318249;