17-8087771-C-T

Variant names:

• chr17-8087771-C-T
• rs3027309
• NM_001139.3:c.-329G>A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001139.3(ALOX12B):​c.-329G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 472,870 control chromosomes in the GnomAD database, including 8,043 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (2059 hom., cov: 32)
  • Exomes 𝑓: 0.19 (5984 hom.)
• Consequence: ALOX12B NM_001139.3 upstream_gene
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.121
• Publications: 3 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

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP6: Variant 17-8087771-C-T is Benign according to our data. Variant chr17-8087771-C-T is described in ClinVar as Benign. ClinVar VariationId is 1271783.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.21 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.-329G>A		upstream_gene	N/A	NP_001130.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX12B	ENST00000647874.1	MANE Select	c.-329G>A		upstream_gene	N/A	ENSP00000497784.1

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23380 AN: 151948 Hom.: 2053 Cov.: 32

Gnomad AFR AF: 0.0733

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.151

GnomAD4 exome AF: 0.188 AC: 60224 AN: 320804 Hom.: 5984 AF XY: 0.191 AC XY: 31878 AN XY: 166854

African (AFR) AF: 0.0733 AC: 756 AN: 10314

American (AMR) AF: 0.190 AC: 2774 AN: 14592

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 1136 AN: 10764

East Asian (EAS) AF: 0.165 AC: 3564 AN: 21620

South Asian (SAS) AF: 0.234 AC: 9627 AN: 41084

European-Finnish (FIN) AF: 0.184 AC: 2657 AN: 14414

Middle Eastern (MID) AF: 0.131 AC: 177 AN: 1352

European-Non Finnish (NFE) AF: 0.193 AC: 36265 AN: 187778

Other (OTH) AF: 0.173 AC: 3268 AN: 18886

GnomAD4 genome AF: 0.154 AC: 23408 AN: 152066 Hom.: 2059 Cov.: 32 AF XY: 0.156 AC XY: 11558 AN XY: 74320

African (AFR) AF: 0.0735 AC: 3049 AN: 41492

American (AMR) AF: 0.191 AC: 2922 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 390 AN: 3468

East Asian (EAS) AF: 0.147 AC: 761 AN: 5174

South Asian (SAS) AF: 0.221 AC: 1068 AN: 4826

European-Finnish (FIN) AF: 0.176 AC: 1859 AN: 10576

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12891 AN: 67942

Other (OTH) AF: 0.156 AC: 329 AN: 2110

Alfa AF: 0.0850 Hom.: 194

Bravo AF: 0.150

Asia WGS AF: 0.176 AC: 614 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	16
DANN	Benign	0.82
PhyloP100		0.12
PromoterAI		-0.050	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3027309; hg19: chr17-7991089;