chr2-214986579-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_173076.3(ABCA12):c.4126T>C(p.Leu1376Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 1,613,664 control chromosomes in the GnomAD database, including 15,717 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3909 hom., cov: 32)

Exomes 𝑓: 0.11 ( 11808 hom. )

Consequence

ABCA12
NM_173076.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 1.97

Publications

11 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: G2P, Genomics England PanelApp, Orphanet
autosomal recessive congenital ichthyosis 4A
Inheritance: AR Classification: STRONG Submitted by: 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 2-214986579-A-G is Benign according to our data. Variant chr2-214986579-A-G is described in ClinVar as Benign. ClinVar VariationId is 262827.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.97 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173076.3. 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.4126T>C	p.Leu1376Leu	synonymous	Exon 28 of 53	NP_775099.2
ABCA12	NM_015657.4		c.3172T>C	p.Leu1058Leu	synonymous	Exon 20 of 45	NP_056472.2
ABCA12	NR_103740.2		n.4624T>C		non_coding_transcript_exon	Exon 30 of 55

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA12	ENST00000272895.12	TSL:1 MANE Select	c.4126T>C	p.Leu1376Leu	synonymous	Exon 28 of 53	ENSP00000272895.7	Q86UK0-1
	ABCA12	ENST00000389661.4	TSL:1	c.3172T>C	p.Leu1058Leu	synonymous	Exon 20 of 45	ENSP00000374312.4	Q86UK0-2

Frequencies

GnomAD3 genomes

AF:

0.185

AC:

28163

AN:

152014

Hom.:

3891

Cov.:

show subpopulations

Gnomad AFR

AF:

0.374

Gnomad AMI

AF:

0.138

Gnomad AMR

AF:

0.241

Gnomad ASJ

AF:

0.136

Gnomad EAS

AF:

0.0441

Gnomad SAS

AF:

0.164

Gnomad FIN

AF:

0.0341

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.0964

Gnomad OTH

AF:

0.196

GnomAD2 exomes

AF:

0.137

AC:

34549

AN:

251318

AF XY:

0.131

show subpopulations

Gnomad AFR exome

AF:

0.387

Gnomad AMR exome

AF:

0.249

Gnomad ASJ exome

AF:

0.142

Gnomad EAS exome

AF:

0.0377

Gnomad FIN exome

AF:

0.0358

Gnomad NFE exome

AF:

0.0957

Gnomad OTH exome

AF:

0.146

GnomAD4 exome

AF:

0.111

AC:

162906

AN:

1461532

Hom.:

11808

Cov.:

AF XY:

0.112

AC XY:

81478

AN XY:

727078

show subpopulations

African (AFR)

AF:

0.389

AC:

13023

AN:

33468

American (AMR)

AF:

0.251

AC:

11214

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.146

AC:

3805

AN:

26130

East Asian (EAS)

AF:

0.0499

AC:

1981

AN:

39692

South Asian (SAS)

AF:

0.166

AC:

14339

AN:

86244

European-Finnish (FIN)

AF:

0.0350

AC:

1867

AN:

53418

Middle Eastern (MID)

AF:

0.217

AC:

1249

AN:

5768

European-Non Finnish (NFE)

AF:

0.0967

AC:

107486

AN:

1111708

Other (OTH)

AF:

0.132

AC:

7942

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

7347

14695

22042

29390

36737

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4284

8568

12852

17136

21420

<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:

0.186

AC:

28221

AN:

152132

Hom.:

3909

Cov.:

AF XY:

0.183

AC XY:

13603

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.375

AC:

15530

AN:

41458

American (AMR)

AF:

0.241

AC:

3687

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.136

AC:

473

AN:

3468

East Asian (EAS)

AF:

0.0440

AC:

228

AN:

5180

South Asian (SAS)

AF:

0.163

AC:

785

AN:

4814

European-Finnish (FIN)

AF:

0.0341

AC:

362

AN:

10608

Middle Eastern (MID)

AF:

0.221

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0964

AC:

6555

AN:

68016

Other (OTH)

AF:

0.194

AC:

410

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1057

2114

3172

4229

5286

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

272

544

816

1088

1360

<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:

0.146

Hom.:

1447

Bravo

AF:

0.209

Asia WGS

AF:

0.107

AC:

373

AN:

3478

EpiCase

AF:

0.112

EpiControl

AF:

0.109

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (2)

Autosomal recessive congenital ichthyosis 4A (1)

Autosomal recessive congenital ichthyosis 4B (1)

Congenital ichthyosis of skin (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

6.5

(source)

DANN

Benign

0.81

PhyloP100

2.0

Mutation Taster

=99/1

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

Computational scores

Splicing

Publications

Other links and lift over