13-30744264-T-C

Variant names:

• chr13-30744264-T-C
• rs3803278
• NM_001629.4:c.170+105T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001629.4(ALOX5AP):​c.170+105T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 1,012,248 control chromosomes in the GnomAD database, including 29,809 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.21 (3671 hom., cov: 32)
  • Exomes 𝑓: 0.24 (26138 hom.)
• Consequence: ALOX5AP NM_001629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.615
• Publications: 7 publications found

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]

LOC124903146 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX5AP	NM_001629.4	c.170+105T>C		intron_variant	Intron 2 of 4	ENST00000380490.5	NP_001620.2
ALOX5AP	NM_001204406.2	c.341+105T>C		intron_variant	Intron 3 of 5		NP_001191335.1
ALOX5AP	XM_017020522.3	c.-71+105T>C		intron_variant	Intron 1 of 4		XP_016876011.1
LOC124903146	XR_007063743.1	n.220+245A>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX5AP	ENST00000380490.5	c.170+105T>C		intron_variant	Intron 2 of 4	1	NM_001629.4	ENSP00000369858.3
ALOX5AP	ENST00000617770.4	c.341+105T>C		intron_variant	Intron 3 of 5	1		ENSP00000479870.1
ALOX5AP	ENST00000479597.1	n.415T>C		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31610 AN: 151978 Hom.: 3666 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.231

GnomAD4 exome AF: 0.240 AC: 206460 AN: 860154 Hom.: 26138 Cov.: 11 AF XY: 0.243 AC XY: 106554 AN XY: 439228

African (AFR) AF: 0.118 AC: 2471 AN: 20966

American (AMR) AF: 0.282 AC: 9113 AN: 32348

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 5056 AN: 20234

East Asian (EAS) AF: 0.429 AC: 13998 AN: 32594

South Asian (SAS) AF: 0.294 AC: 19893 AN: 67610

European-Finnish (FIN) AF: 0.230 AC: 10010 AN: 43610

Middle Eastern (MID) AF: 0.225 AC: 760 AN: 3380

European-Non Finnish (NFE) AF: 0.226 AC: 135669 AN: 600094

Other (OTH) AF: 0.241 AC: 9490 AN: 39318

GnomAD4 genome AF: 0.208 AC: 31632 AN: 152094 Hom.: 3671 Cov.: 32 AF XY: 0.213 AC XY: 15838 AN XY: 74322

African (AFR) AF: 0.116 AC: 4819 AN: 41506

American (AMR) AF: 0.251 AC: 3833 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 883 AN: 3468

East Asian (EAS) AF: 0.410 AC: 2112 AN: 5152

South Asian (SAS) AF: 0.307 AC: 1476 AN: 4814

European-Finnish (FIN) AF: 0.224 AC: 2370 AN: 10568

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15460 AN: 67988

Other (OTH) AF: 0.235 AC: 497 AN: 2112

Alfa AF: 0.208 Hom.: 550

Bravo AF: 0.207

Asia WGS AF: 0.360 AC: 1251 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.7
DANN	Benign	0.74
PhyloP100		0.61
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3803278; hg19: chr13-31318401; COSMIC: COSV66857730;