Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000272895.12(ABCA12):c.2124A>G(p.Ala708Ala) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 1,613,406 control chromosomes in the GnomAD database, including 24,124 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 8799 hom., cov: 32)

Exomes 𝑓: 0.11 ( 15325 hom. )

Consequence

ABCA12
ENST00000272895.12 splice_region, synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.716

Publications

14 publications found

Variant links:

Genes affected

ABCA12 (HGNC:14637): (ATP binding cassette subfamily A member 12) The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intracellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, and White). This encoded protein is a member of the ABC1 subfamily, which is the only major ABC subfamily found exclusively in multicellular eukaryotes. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]

ABCA12 Gene-Disease associations (from GenCC):

autosomal recessive congenital ichthyosis 4B
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, PanelApp Australia, Orphanet, G2P
autosomal recessive congenital ichthyosis 4A
Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
congenital non-bullous ichthyosiform erythroderma
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
lamellar ichthyosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ABCA12 links:

ENSG00000227769 (HGNC:):

ENSG00000227769 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 2-215011647-T-C is Benign according to our data. Variant chr2-215011647-T-C is described in ClinVar as Benign. ClinVar VariationId is 262823.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.716 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000272895.12. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ABCA12	NM_173076.3	MANE Select	c.2124A>G	p.Ala708Ala	splice_region synonymous	Exon 17 of 53	NP_775099.2
ABCA12	NM_015657.4		c.1170A>G	p.Ala390Ala	splice_region synonymous	Exon 9 of 45	NP_056472.2
ABCA12	NR_103740.2		n.2566A>G		splice_region non_coding_transcript_exon	Exon 18 of 55

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ABCA12	ENST00000272895.12	TSL:1 MANE Select	c.2124A>G	p.Ala708Ala	splice_region synonymous	Exon 17 of 53	ENSP00000272895.7
ABCA12	ENST00000389661.4	TSL:1	c.1170A>G	p.Ala390Ala	splice_region synonymous	Exon 9 of 45	ENSP00000374312.4
ENSG00000227769	ENST00000617699.1	TSL:5	n.29-1409T>C		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.249

AC:

37782

AN:

151928

Hom.:

8762

Cov.:

show subpopulations

Gnomad AFR

AF:

0.612

Gnomad AMI

AF:

0.145

Gnomad AMR

AF:

0.263

Gnomad ASJ

AF:

0.123

Gnomad EAS

AF:

0.0473

Gnomad SAS

AF:

0.164

Gnomad FIN

AF:

0.0328

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.0880

Gnomad OTH

AF:

0.239

GnomAD2 exomes

AF:

0.150

AC:

37605

AN:

251246

AF XY:

0.138

show subpopulations

Gnomad AFR exome

AF:

0.624

Gnomad AMR exome

AF:

0.254

Gnomad ASJ exome

AF:

0.123

Gnomad EAS exome

AF:

0.0414

Gnomad FIN exome

AF:

0.0340

Gnomad NFE exome

AF:

0.0886

Gnomad OTH exome

AF:

0.153

GnomAD4 exome

AF:

0.111

AC:

161661

AN:

1461360

Hom.:

15325

Cov.:

AF XY:

0.110

AC XY:

80188

AN XY:

727008

show subpopulations

African (AFR)

AF:

0.634

AC:

21202

AN:

33460

American (AMR)

AF:

0.257

AC:

11504

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.127

AC:

3327

AN:

26134

East Asian (EAS)

AF:

0.0552

AC:

2191

AN:

39684

South Asian (SAS)

AF:

0.165

AC:

14196

AN:

86248

European-Finnish (FIN)

AF:

0.0331

AC:

1770

AN:

53418

Middle Eastern (MID)

AF:

0.232

AC:

1341

AN:

5768

European-Non Finnish (NFE)

AF:

0.0879

AC:

97752

AN:

1111550

Other (OTH)

AF:

0.139

AC:

8378

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

7242

14484

21725

28967

36209

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4010

8020

12030

16040

20050

<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:

0.249

AC:

37872

AN:

152046

Hom.:

8799

Cov.:

AF XY:

0.245

AC XY:

18239

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.613

AC:

25366

AN:

41406

American (AMR)

AF:

0.264

AC:

4024

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.123

AC:

426

AN:

3472

East Asian (EAS)

AF:

0.0472

AC:

244

AN:

5168

South Asian (SAS)

AF:

0.163

AC:

785

AN:

4820

European-Finnish (FIN)

AF:

0.0328

AC:

348

AN:

10608

Middle Eastern (MID)

AF:

0.235

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0879

AC:

5979

AN:

67998

Other (OTH)

AF:

0.236

AC:

499

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1013

2026

3039

4052

5065

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

318

636

954

1272

1590

<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:

0.152

Hom.:

5040

Bravo

AF:

0.281

Asia WGS

AF:

0.124

AC:

433

AN:

3478

EpiCase

AF:

0.102

EpiControl

AF:

0.102

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Congenital ichthyosis of skin (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.20

(source)

DANN

Benign

0.51

PhyloP100

-0.72

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over