2-214989432-C-T

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.3726G>A(p.Pro1242Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0607 in 1,612,962 control chromosomes in the GnomAD database, including 3,887 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P1242P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.074 ( 550 hom., cov: 30)

Exomes 𝑓: 0.059 ( 3337 hom. )

Consequence

ABCA12
NM_173076.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.554

Publications

8 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=-0.37).

BP6

Variant 2-214989432-C-T is Benign according to our data. Variant chr2-214989432-C-T is described in ClinVar as Benign. ClinVar VariationId is 262826.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.554 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.156 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.3726G>A	p.Pro1242Pro	synonymous	Exon 26 of 53	NP_775099.2
ABCA12	NM_015657.4		c.2772G>A	p.Pro924Pro	synonymous	Exon 18 of 45	NP_056472.2
ABCA12	NR_103740.2		n.4224G>A		non_coding_transcript_exon	Exon 28 of 55

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA12	ENST00000272895.12	TSL:1 MANE Select	c.3726G>A	p.Pro1242Pro	synonymous	Exon 26 of 53	ENSP00000272895.7	Q86UK0-1
	ABCA12	ENST00000389661.4	TSL:1	c.2772G>A	p.Pro924Pro	synonymous	Exon 18 of 45	ENSP00000374312.4	Q86UK0-2

Frequencies

GnomAD3 genomes

AF:

0.0740

AC:

11178

AN:

151076

Hom.:

544

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0959

Gnomad AMI

AF:

0.0771

Gnomad AMR

AF:

0.160

Gnomad ASJ

AF:

0.0968

Gnomad EAS

AF:

0.00117

Gnomad SAS

AF:

0.0480

Gnomad FIN

AF:

0.0255

Gnomad MID

AF:

0.122

Gnomad NFE

AF:

0.0544

Gnomad OTH

AF:

0.0902

GnomAD2 exomes

AF:

0.0723

AC:

18183

AN:

251464

AF XY:

0.0672

show subpopulations

Gnomad AFR exome

AF:

0.103

Gnomad AMR exome

AF:

0.196

Gnomad ASJ exome

AF:

0.103

Gnomad EAS exome

AF:

0.000218

Gnomad FIN exome

AF:

0.0247

Gnomad NFE exome

AF:

0.0533

Gnomad OTH exome

AF:

0.0821

GnomAD4 exome

AF:

0.0593

AC:

86689

AN:

1461772

Hom.:

3337

Cov.:

AF XY:

0.0586

AC XY:

42618

AN XY:

727198

show subpopulations

African (AFR)

AF:

0.104

AC:

3487

AN:

33480

American (AMR)

AF:

0.193

AC:

8620

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.105

AC:

2733

AN:

26136

East Asian (EAS)

AF:

0.000227

AC:

AN:

39696

South Asian (SAS)

AF:

0.0520

AC:

4483

AN:

86254

European-Finnish (FIN)

AF:

0.0243

AC:

1299

AN:

53412

Middle Eastern (MID)

AF:

0.112

AC:

644

AN:

5768

European-Non Finnish (NFE)

AF:

0.0552

AC:

61372

AN:

1111914

Other (OTH)

AF:

0.0669

AC:

4042

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

4425

8850

13275

17700

22125

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2456

4912

7368

9824

12280

<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:

0.0741

AC:

11200

AN:

151190

Hom.:

550

Cov.:

AF XY:

0.0739

AC XY:

5453

AN XY:

73796

show subpopulations

African (AFR)

AF:

0.0958

AC:

3947

AN:

41202

American (AMR)

AF:

0.161

AC:

2439

AN:

15124

Ashkenazi Jewish (ASJ)

AF:

0.0968

AC:

335

AN:

3460

East Asian (EAS)

AF:

0.00117

AC:

AN:

5114

South Asian (SAS)

AF:

0.0478

AC:

229

AN:

4786

European-Finnish (FIN)

AF:

0.0255

AC:

265

AN:

10402

Middle Eastern (MID)

AF:

0.117

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0544

AC:

3688

AN:

67822

Other (OTH)

AF:

0.0898

AC:

187

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

490

980

1470

1960

2450

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

118

236

354

472

590

<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:

0.0743

Hom.:

476

Bravo

AF:

0.0861

Asia WGS

AF:

0.0310

AC:

106

AN:

3478

EpiCase

AF:

0.0606

EpiControl

AF:

0.0602

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 4A (1)

Autosomal recessive congenital ichthyosis 4B (1)

Congenital ichthyosis of skin (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

1.6

(source)

DANN

Benign

0.56

PhyloP100

-0.55

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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