dbSNP rs2304908: ALOX12B:c.650+7C>G (chr17-8080651-G-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Variant links:

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, Labcorp Genetics (formerly Invitae), G2P
congenital non-bullous ichthyosiform erythroderma
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet
lamellar ichthyosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
self-healing collodion baby
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ALOX12B links:

ENSG00000214999 (HGNC:):

ENSG00000214999 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Sel.	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	O75342

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ALOX12B	ENST00000647874.1	MANE Select	c.650+7C>G	splice_region intron	N/A	ENSP00000497784.1	O75342
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.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.343

AC XY:

249123

AN XY:

727122

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

20437

40874

61310

81747

102184

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11980

23960

35940

47920

59900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.416

AC:

63165

AN:

151964

Hom.:

14172

Cov.:

AF XY:

0.415

AC XY:

30814

AN XY:

74276

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.324

AC:

22024

AN:

67950

Other (OTH)

AF:

0.396

AC:

835

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1766

3533

5299

7066

8832

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

570

1140

1710

2280

2850

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Autosomal recessive congenital ichthyosis 2 (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

3.9

(source)

DANN

Benign

0.84

PhyloP100

-0.97

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over