17-8072652-G-GT

Position:

• chr17-8072652-G-GT

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_Supporting BS2

The NM_001139.3(ALOX12B):​c.*118_*119insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00164 in 1,438,474 control chromosomes in the GnomAD database, including 10 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (6 hom.)
• Consequence: ALOX12B NM_001139.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.264

Genes affected

ALOX12B (HGNC:430): (arachidonate 12-lipoxygenase, 12R type) This gene encodes an enzyme involved in the conversion of arachidonic acid to 12R-hydroxyeicosatetraenoic acid. Mutations in this gene are associated with nonbullous congenital ichthyosiform erythroderma. [provided by RefSeq, Sep 2015]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00194 (295/152322) while in subpopulation SAS AF= 0.00249 (12/4826). AF 95% confidence interval is 0.00156. There are 4 homozygotes in gnomad4. There are 174 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALOX12B	NM_001139.3	c.*118_*119insA		3_prime_UTR_variant	15/15	ENST00000647874.1	NP_001130.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALOX12B	ENST00000647874.1	c.*118_*119insA		3_prime_UTR_variant	15/15		NM_001139.3	ENSP00000497784	P1

Frequencies

GnomAD3 genomes AF: 0.00194 AC: 295 AN: 152204 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000289

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.000981

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.0107

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00182

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.00161 AC: 2065 AN: 1286152 Hom.: 6 Cov.: 20 AF XY: 0.00163 AC XY: 1052 AN XY: 645888

Gnomad4 AFR exome AF: 0.000244

Gnomad4 AMR exome AF: 0.00114

Gnomad4 ASJ exome AF: 0.00297

Gnomad4 EAS exome AF: 0.0000259

Gnomad4 SAS exome AF: 0.00165

Gnomad4 FIN exome AF: 0.0110

Gnomad4 NFE exome AF: 0.00117

Gnomad4 OTH exome AF: 0.00186

GnomAD4 genome AF: 0.00194 AC: 295 AN: 152322 Hom.: 4 Cov.: 32 AF XY: 0.00234 AC XY: 174 AN XY: 74486

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.000980

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.0107

Gnomad4 NFE AF: 0.00182

Gnomad4 OTH AF: 0.000473

Bravo AF: 0.00116

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital ichthyosiform erythroderma Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs558690816; hg19: chr17-7975970;