rs16853022

Variant names:

Variant summary

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

The NM_173076.3(ABCA12):c.5400G>A(p.Thr1800Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0333 in 1,613,800 control chromosomes in the GnomAD database, including 3,845 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.094 ( 1732 hom., cov: 33)

Exomes 𝑓: 0.027 ( 2113 hom. )

Consequence

ABCA12
NM_173076.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.999

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 2-214974846-C-T is Benign according to our data. Variant chr2-214974846-C-T is described in ClinVar as Benign. ClinVar VariationId is 262829.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.999 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.274 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.5400G>A	p.Thr1800Thr	synonymous	Exon 35 of 53	NP_775099.2
ABCA12	NM_015657.4		c.4446G>A	p.Thr1482Thr	synonymous	Exon 27 of 45	NP_056472.2
ABCA12	NR_103740.2		n.5898G>A		non_coding_transcript_exon	Exon 37 of 55

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA12	ENST00000272895.12	TSL:1 MANE Select	c.5400G>A	p.Thr1800Thr	synonymous	Exon 35 of 53	ENSP00000272895.7	Q86UK0-1
	ABCA12	ENST00000389661.4	TSL:1	c.4446G>A	p.Thr1482Thr	synonymous	Exon 27 of 45	ENSP00000374312.4	Q86UK0-2

Frequencies

GnomAD3 genomes

AF:

0.0941

AC:

14304

AN:

152060

Hom.:

1727

Cov.:

show subpopulations

Gnomad AFR

AF:

0.278

Gnomad AMI

AF:

0.0537

Gnomad AMR

AF:

0.0519

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.0418

Gnomad SAS

AF:

0.0857

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0156

Gnomad OTH

AF:

0.0861

GnomAD2 exomes

AF:

0.0423

AC:

10629

AN:

251308

AF XY:

0.0399

show subpopulations

Gnomad AFR exome

AF:

0.291

Gnomad AMR exome

AF:

0.0240

Gnomad ASJ exome

AF:

0.0105

Gnomad EAS exome

AF:

0.0353

Gnomad FIN exome

AF:

0.00319

Gnomad NFE exome

AF:

0.0157

Gnomad OTH exome

AF:

0.0344

GnomAD4 exome

AF:

0.0270

AC:

39428

AN:

1461622

Hom.:

2113

Cov.:

AF XY:

0.0278

AC XY:

20233

AN XY:

727124

show subpopulations

African (AFR)

AF:

0.290

AC:

9695

AN:

33442

American (AMR)

AF:

0.0276

AC:

1233

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0103

AC:

269

AN:

26132

East Asian (EAS)

AF:

0.0540

AC:

2142

AN:

39688

South Asian (SAS)

AF:

0.0782

AC:

6748

AN:

86248

European-Finnish (FIN)

AF:

0.00294

AC:

157

AN:

53410

Middle Eastern (MID)

AF:

0.0607

AC:

350

AN:

5764

European-Non Finnish (NFE)

AF:

0.0149

AC:

16572

AN:

1111838

Other (OTH)

AF:

0.0375

AC:

2262

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

1904

3808

5711

7615

9519

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

826

1652

2478

3304

4130

<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:

0.0942

AC:

14337

AN:

152178

Hom.:

1732

Cov.:

AF XY:

0.0927

AC XY:

6901

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.279

AC:

11559

AN:

41504

American (AMR)

AF:

0.0519

AC:

793

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00749

AC:

AN:

3472

East Asian (EAS)

AF:

0.0417

AC:

216

AN:

5176

South Asian (SAS)

AF:

0.0864

AC:

416

AN:

4816

European-Finnish (FIN)

AF:

0.00179

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0156

AC:

1063

AN:

68006

Other (OTH)

AF:

0.0848

AC:

179

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

549

1098

1648

2197

2746

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

276

414

552

690

<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:

0.0427

Hom.:

1040

Bravo

AF:

0.106

Asia WGS

AF:

0.0630

AC:

220

AN:

3478

EpiCase

AF:

0.0206

EpiControl

AF:

0.0206

ClinVar

ClinVar submissions

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

-0.82

CADD

Benign

0.87

(source)

DANN

Benign

0.34

PhyloP100

-1.0

Mutation Taster

=100/0

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

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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