Genetic Variant ABCA12:c.5690+321T>C (chr2-214969952-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_173076.3(ABCA12):c.5690+321T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 151,728 control chromosomes in the GnomAD database, including 19,380 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.50 ( 19380 hom., cov: 31)

Consequence

ABCA12
NM_173076.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.774

Publications

3 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
ABCA12	NM_173076.3 link	c.5690+321T>C	intron_variant	Intron 37 of 52	ENST00000272895.12	NP_775099.2
ABCA12	NM_015657.4 link	c.4736+321T>C	intron_variant	Intron 29 of 44		NP_056472.2
ABCA12	NR_103740.2 link	n.6188+321T>C	intron_variant	Intron 39 of 54
ABCA12	XM_011510951.3 link	c.5699+321T>C	intron_variant	Intron 37 of 52		XP_011509253.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA12	ENST00000272895.12 link	c.5690+321T>C		intron_variant	Intron 37 of 52	1	NM_173076.3	ENSP00000272895.7
ABCA12	ENST00000389661.4 link	c.4736+321T>C		intron_variant	Intron 29 of 44	1		ENSP00000374312.4

Frequencies

GnomAD3 genomes

AF:

0.502

AC:

76172

AN:

151612

Hom.:

19354

Cov.:

show subpopulations

Gnomad AFR

AF:

0.483

Gnomad AMI

AF:

0.576

Gnomad AMR

AF:

0.540

Gnomad ASJ

AF:

0.506

Gnomad EAS

AF:

0.267

Gnomad SAS

AF:

0.520

Gnomad FIN

AF:

0.544

Gnomad MID

AF:

0.497

Gnomad NFE

AF:

0.516

Gnomad OTH

AF:

0.484

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.503

AC:

76245

AN:

151728

Hom.:

19380

Cov.:

AF XY:

0.503

AC XY:

37281

AN XY:

74108

show subpopulations

African (AFR)

AF:

0.483

AC:

20000

AN:

41408

American (AMR)

AF:

0.540

AC:

8233

AN:

15242

Ashkenazi Jewish (ASJ)

AF:

0.506

AC:

1752

AN:

3462

East Asian (EAS)

AF:

0.266

AC:

1374

AN:

5158

South Asian (SAS)

AF:

0.521

AC:

2506

AN:

4810

European-Finnish (FIN)

AF:

0.544

AC:

5727

AN:

10532

Middle Eastern (MID)

AF:

0.507

AC:

149

AN:

294

European-Non Finnish (NFE)

AF:

0.516

AC:

34963

AN:

67802

Other (OTH)

AF:

0.482

AC:

1017

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1920

3839

5759

7678

9598

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

694

1388

2082

2776

3470

<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:

0.499

Hom.:

9458

Bravo

AF:

0.495

Asia WGS

AF:

0.396

AC:

1377

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

9.5

(source)

DANN

Benign

0.90

PhyloP100

0.77

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over