NM_173076.3:c.888G>A

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.888G>A(p.Val296Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 1,612,510 control chromosomes in the GnomAD database, including 37,283 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 2995 hom., cov: 32)

Exomes 𝑓: 0.21 ( 34288 hom. )

Consequence

ABCA12
NM_173076.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.189

Publications

12 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=-0.56).

BP6

Variant 2-215037050-C-T is Benign according to our data. Variant chr2-215037050-C-T is described in ClinVar as Benign. ClinVar VariationId is 262834.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.189 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.387 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA12	NM_173076.3	MANE Select	c.888G>A	p.Val296Val	synonymous	Exon 8 of 53	NP_775099.2
	ABCA12	NR_103740.2		n.1330G>A		non_coding_transcript_exon	Exon 9 of 55

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ABCA12	ENST00000272895.12	TSL:1 MANE Select	c.888G>A	p.Val296Val	synonymous	Exon 8 of 53	ENSP00000272895.7
ENSG00000227769	ENST00000419251.3	TSL:5	n.706+1217C>T		intron	N/A
ENSG00000227769	ENST00000437897.7	TSL:5	n.1016+1217C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.191

AC:

29031

AN:

151974

Hom.:

3001

Cov.:

show subpopulations

Gnomad AFR

AF:

0.147

Gnomad AMI

AF:

0.241

Gnomad AMR

AF:

0.220

Gnomad ASJ

AF:

0.206

Gnomad EAS

AF:

0.402

Gnomad SAS

AF:

0.132

Gnomad FIN

AF:

0.167

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.201

Gnomad OTH

AF:

0.204

GnomAD2 exomes

AF:

0.212

AC:

53177

AN:

251314

AF XY:

0.205

show subpopulations

Gnomad AFR exome

AF:

0.150

Gnomad AMR exome

AF:

0.286

Gnomad ASJ exome

AF:

0.193

Gnomad EAS exome

AF:

0.395

Gnomad FIN exome

AF:

0.166

Gnomad NFE exome

AF:

0.201

Gnomad OTH exome

AF:

0.206

GnomAD4 exome

AF:

0.209

AC:

305910

AN:

1460418

Hom.:

34288

Cov.:

AF XY:

0.206

AC XY:

149795

AN XY:

726594

show subpopulations

African (AFR)

AF:

0.145

AC:

4842

AN:

33458

American (AMR)

AF:

0.281

AC:

12571

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.194

AC:

5072

AN:

26120

East Asian (EAS)

AF:

0.442

AC:

17538

AN:

39644

South Asian (SAS)

AF:

0.130

AC:

11252

AN:

86236

European-Finnish (FIN)

AF:

0.167

AC:

8927

AN:

53380

Middle Eastern (MID)

AF:

0.149

AC:

859

AN:

5764

European-Non Finnish (NFE)

AF:

0.209

AC:

232197

AN:

1110754

Other (OTH)

AF:

0.210

AC:

12652

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

11197

22394

33590

44787

55984

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8276

16552

24828

33104

41380

<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:

0.191

AC:

29029

AN:

152092

Hom.:

2995

Cov.:

AF XY:

0.190

AC XY:

14093

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.147

AC:

6081

AN:

41480

American (AMR)

AF:

0.220

AC:

3364

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.206

AC:

715

AN:

3470

East Asian (EAS)

AF:

0.402

AC:

2075

AN:

5168

South Asian (SAS)

AF:

0.132

AC:

638

AN:

4822

European-Finnish (FIN)

AF:

0.167

AC:

1768

AN:

10560

Middle Eastern (MID)

AF:

0.163

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.201

AC:

13689

AN:

67996

Other (OTH)

AF:

0.204

AC:

431

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1176

2352

3529

4705

5881

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

306

612

918

1224

1530

<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:

0.202

Hom.:

8837

Bravo

AF:

0.198

Asia WGS

AF:

0.277

AC:

963

AN:

3478

EpiCase

AF:

0.199

EpiControl

AF:

0.201

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

-0.56

CADD

Benign

4.6

(source)

DANN

Benign

0.70

PhyloP100

0.19

Mutation Taster

=100/0

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over