17-8080651-G-C

Variant names:

• chr17-8080651-G-C
• rs2304908
• NM_001139.3:c.650+7C>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001139.3(ALOX12B):​c.650+7C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 1,613,600 control chromosomes in the GnomAD database, including 103,332 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (14172 hom., cov: 32)
  • Exomes 𝑓: 0.34 (89160 hom.)
• Consequence: ALOX12B NM_001139.3 splice_region, intron
• Scores: Splicing: ADA: 0.00006547
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.969

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]

ENSG00000214999 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 17-8080651-G-C is Benign according to our data. Variant chr17-8080651-G-C is described in ClinVar as [Benign]. Clinvar id is 257554.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-8080651-G-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX12B	NM_001139.3	c.650+7C>G		splice_region_variant, intron_variant	Intron 5 of 14	ENST00000647874.1	NP_001130.1
LOC107985075	XR_001752778.2	n.924G>C		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX12B	ENST00000647874.1	c.650+7C>G		splice_region_variant, intron_variant	Intron 5 of 14		NM_001139.3	ENSP00000497784.1
ENSG00000214999	ENST00000399413.3	n.890G>C		non_coding_transcript_exon_variant	Exon 2 of 2	1

Frequencies

GnomAD3 genomes AF: 0.415 AC: 63069 AN: 151846 Hom.: 14139 Cov.: 32

Gnomad AFR AF: 0.591

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.391

GnomAD3 exomes AF: 0.380 AC: 95537 AN: 251214 Hom.: 19490 AF XY: 0.367 AC XY: 49871 AN XY: 135790

Gnomad AFR exome AF: 0.599

Gnomad AMR exome AF: 0.518

Gnomad ASJ exome AF: 0.317

Gnomad EAS exome AF: 0.386

Gnomad SAS exome AF: 0.364

Gnomad FIN exome AF: 0.390

Gnomad NFE exome AF: 0.317

Gnomad OTH exome AF: 0.342

GnomAD4 exome AF: 0.344 AC: 502589 AN: 1461636 Hom.: 89160 Cov.: 48 AF XY: 0.343 AC XY: 249123 AN XY: 727122

Gnomad4 AFR exome AF: 0.602

Gnomad4 AMR exome AF: 0.507

Gnomad4 ASJ exome AF: 0.317

Gnomad4 EAS exome AF: 0.410

Gnomad4 SAS exome AF: 0.361

Gnomad4 FIN exome AF: 0.389

Gnomad4 NFE exome AF: 0.324

Gnomad4 OTH exome AF: 0.356

GnomAD4 genome AF: 0.416 AC: 63165 AN: 151964 Hom.: 14172 Cov.: 32 AF XY: 0.415 AC XY: 30814 AN XY: 74276

Gnomad4 AFR AF: 0.591

Gnomad4 AMR AF: 0.426

Gnomad4 ASJ AF: 0.329

Gnomad4 EAS AF: 0.404

Gnomad4 SAS AF: 0.352

Gnomad4 FIN AF: 0.384

Gnomad4 NFE AF: 0.324

Gnomad4 OTH AF: 0.396

Alfa AF: 0.349 Hom.: 3223

Bravo AF: 0.429

Asia WGS AF: 0.435 AC: 1511 AN: 3478

EpiCase AF: 0.303

EpiControl AF: 0.298

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive congenital ichthyosis 2 Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	3.9
DANN	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000065
dbscSNV1_RF	Benign	0.0
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: rs2304908; hg19: chr17-7983969; COSMIC: COSV59870751; COSMIC: COSV59870751;