17-8080651-G-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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]

ALOX12B Gene-Disease associations (from GenCC):

• autosomal recessive congenital ichthyosis 2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
• congenital non-bullous ichthyosiform erythroderma

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
• lamellar ichthyosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• self-healing collodion baby

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000214999 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 257554.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001139.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX12B	NM_001139.3	MANE Select	c.650+7C>G		splice_region intron	N/A	NP_001130.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX12B	ENST00000647874.1	MANE Select	c.650+7C>G		splice_region intron	N/A	ENSP00000497784.1
	ENSG00000214999	ENST00000399413.3	TSL:1	n.890G>C		non_coding_transcript_exon	Exon 2 of 2
	ENSG00000214999	ENST00000763133.1		n.55-543G>C		intron	N/A

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

GnomAD2 exomes AF: 0.380 AC: 95537 AN: 251214 AF XY: 0.367

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 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

African (AFR) AF: 0.602 AC: 20147 AN: 33474

American (AMR) AF: 0.507 AC: 22672 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 8297 AN: 26134

East Asian (EAS) AF: 0.410 AC: 16288 AN: 39698

South Asian (SAS) AF: 0.361 AC: 31164 AN: 86210

European-Finnish (FIN) AF: 0.389 AC: 20768 AN: 53402

Middle Eastern (MID) AF: 0.276 AC: 1577 AN: 5724

European-Non Finnish (NFE) AF: 0.324 AC: 360170 AN: 1111906

Other (OTH) AF: 0.356 AC: 21506 AN: 60374

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

African (AFR) AF: 0.591 AC: 24484 AN: 41418

American (AMR) AF: 0.426 AC: 6512 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1141 AN: 3472

East Asian (EAS) AF: 0.404 AC: 2078 AN: 5148

South Asian (SAS) AF: 0.352 AC: 1694 AN: 4818

European-Finnish (FIN) AF: 0.384 AC: 4053 AN: 10568

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.324 AC: 22024 AN: 67950

Other (OTH) AF: 0.396 AC: 835 AN: 2110

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Autosomal recessive congenital ichthyosis 2 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	3.9
DANN	Benign	0.84
PhyloP100		-0.97
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2304908; hg19: chr17-7983969; COSMIC: COSV59870751; COSMIC: COSV59870751;