chr17-8044921-C-T

Position:

• chr17-8044921-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001141.3(ALOX15B):​c.769C>T​(p.Leu257Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00519 in 1,614,136 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0038 (2 hom., cov: 31)
  • Exomes 𝑓: 0.0053 (30 hom.)
• Consequence: ALOX15B NM_001141.3 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0920

Genes affected

ALOX15B (HGNC:434): (arachidonate 15-lipoxygenase type B) This gene encodes a member of the lipoxygenase family of structurally related nonheme iron dioxygenases involved in the production of fatty acid hydroperoxides. The encoded protein converts arachidonic acid exclusively to 15S-hydroperoxyeicosatetraenoic acid, while metabolizing linoleic acid less effectively. This gene is located in a cluster of related genes and a pseudogene that spans approximately 100 kilobases on the short arm of chromosome 17. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ALOX15B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.016626567).
• BP6: Variant 17-8044921-C-T is Benign according to our data. Variant chr17-8044921-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 780167.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALOX15B	NM_001141.3	c.769C>T	p.Leu257Phe	missense_variant	6/14	ENST00000380183.9	NP_001132.2
ALOX15B	NM_001039130.2	c.769C>T	p.Leu257Phe	missense_variant	6/13		NP_001034219.1
ALOX15B	NM_001039131.2	c.769C>T	p.Leu257Phe	missense_variant	6/12		NP_001034220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALOX15B	ENST00000380183.9	c.769C>T	p.Leu257Phe	missense_variant	6/14	1	NM_001141.3	ENSP00000369530.4

Frequencies

GnomAD3 genomes AF: 0.00378 AC: 575 AN: 152138 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.00121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00406

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00236

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00625

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00334 AC: 839 AN: 251474 Hom.: 2 AF XY: 0.00326 AC XY: 443 AN XY: 135912

Gnomad AFR exome AF: 0.00105

Gnomad AMR exome AF: 0.00289

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000196

Gnomad FIN exome AF: 0.00203

Gnomad NFE exome AF: 0.00557

Gnomad OTH exome AF: 0.00554

GnomAD4 exome AF: 0.00534 AC: 7810 AN: 1461880 Hom.: 30 Cov.: 36 AF XY: 0.00526 AC XY: 3828 AN XY: 727246

Gnomad4 AFR exome AF: 0.000896

Gnomad4 AMR exome AF: 0.00297

Gnomad4 ASJ exome AF: 0.000344

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000151

Gnomad4 FIN exome AF: 0.00275

Gnomad4 NFE exome AF: 0.00644

Gnomad4 OTH exome AF: 0.00500

GnomAD4 genome AF: 0.00378 AC: 575 AN: 152256 Hom.: 2 Cov.: 31 AF XY: 0.00328 AC XY: 244 AN XY: 74434

Gnomad4 AFR AF: 0.00120

Gnomad4 AMR AF: 0.00405

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00236

Gnomad4 NFE AF: 0.00625

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00511 Hom.: 1

Bravo AF: 0.00385

TwinsUK AF: 0.00431 AC: 16

ALSPAC AF: 0.00519 AC: 20

ESP6500AA AF: 0.00182 AC: 8

ESP6500EA AF: 0.00570 AC: 49

ExAC AF: 0.00322 AC: 391

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00638

EpiControl AF: 0.00516

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely 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
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T;T;.;.
Eigen	Benign	0.042
Eigen_PC	Benign	-0.071
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.83	T;T;T;T
M_CAP	Benign	0.067	D
MetaRNN	Benign	0.017	T;T;T;T
MetaSVM	Benign	-0.30	T
MutationAssessor	Benign	0.88	L;.;L;L
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.2	D;.;D;.
REVEL	Uncertain	0.43
Sift	Uncertain	0.0050	D;.;D;.
Sift4G	Uncertain	0.0080	D;D;D;D
Polyphen		1.0	D;.;D;D
Vest4		0.26
MVP		0.86
MPC		0.66
ClinPred		0.026	T
GERP RS		4.0
Varity_R		0.51
gMVP		0.55

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

Other links and lift over

dbSNP: rs141534086; hg19: chr17-7948239;