NM_001629.4:c.123C>T

Variant names:

• chr13-30744112-C-T
• rs41351946
• NM_001629.4:c.123C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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 -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 rank	MANE	Protein	UniProt
ALOX5AP	NM_001629.4	c.123C>T	p.Ser41Ser	synonymous_variant	Exon 2 of 5	ENST00000380490.5	NP_001620.2
ALOX5AP	NM_001204406.2	c.294C>T	p.Ser98Ser	synonymous_variant	Exon 3 of 6		NP_001191335.1
ALOX5AP	XM_017020522.3	c.-118C>T		5_prime_UTR_variant	Exon 1 of 5		XP_016876011.1
LOC124903146	XR_007063743.1	n.220+397G>A		intron_variant	Intron 2 of 2

Ensembl

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

GnomAD2 exomes AF: 0.00469 AC: 1180 AN: 251420 AF XY: 0.00460

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 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

African (AFR) AF: 0.00161 AC: 54 AN: 33476

American (AMR) AF: 0.00948 AC: 424 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00708 AC: 185 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00104 AC: 90 AN: 86258

European-Finnish (FIN) AF: 0.000955 AC: 51 AN: 53404

Middle Eastern (MID) AF: 0.0149 AC: 86 AN: 5768

European-Non Finnish (NFE) AF: 0.00572 AC: 6361 AN: 1111936

Other (OTH) AF: 0.00580 AC: 350 AN: 60390

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

African (AFR) AF: 0.00154 AC: 64 AN: 41570

American (AMR) AF: 0.0115 AC: 176 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 35 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00104 AC: 11 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00517 AC: 352 AN: 68038

Other (OTH) AF: 0.00851 AC: 18 AN: 2116

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	13
DANN	Benign	0.91
PhyloP100		0.83
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs41351946; hg19: chr13-31318249;