2-214986522-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_173076.3(ABCA12):c.4163+20T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 1 in 1,611,294 control chromosomes in the GnomAD database, including 805,353 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 1.0 ( 76006 hom., cov: 31)

Exomes 𝑓: 1.0 ( 729347 hom. )

Consequence

ABCA12
NM_173076.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.09

Publications

5 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 2-214986522-A-G is Benign according to our data. Variant chr2-214986522-A-G is described in ClinVar as [Benign]. Clinvar id is 262828.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ABCA12	NM_173076.3 link	c.4163+20T>C	intron_variant	Intron 28 of 52	ENST00000272895.12	NP_775099.2	Q86UK0-1B3KVV3
ABCA12	NM_015657.4 link	c.3209+20T>C	intron_variant	Intron 20 of 44		NP_056472.2	Q86UK0-2B3KVV3
ABCA12	NR_103740.2 link	n.4661+20T>C	intron_variant	Intron 30 of 54
ABCA12	XM_011510951.3 link	c.4172+20T>C	intron_variant	Intron 28 of 52		XP_011509253.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA12	ENST00000272895.12 link	c.4163+20T>C		intron_variant	Intron 28 of 52	1	NM_173076.3	ENSP00000272895.7		Q86UK0-1
ABCA12	ENST00000389661.4 link	c.3209+20T>C		intron_variant	Intron 20 of 44	1		ENSP00000374312.4		Q86UK0-2

Frequencies

GnomAD3 genomes

AF:

0.999

AC:

152044

AN:

152192

Hom.:

75949

Cov.:

show subpopulations

Gnomad AFR

AF:

0.997

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

1.00

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.999

GnomAD2 exomes

AF:

1.00

AC:

251094

AN:

251162

AF XY:

1.00

show subpopulations

Gnomad AFR exome

AF:

0.996

Gnomad AMR exome

AF:

1.00

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

1.00

GnomAD4 exome

AF:

1.00

AC:

1458839

AN:

1458984

Hom.:

729347

Cov.:

AF XY:

1.00

AC XY:

726035

AN XY:

726094

show subpopulations

African (AFR)

AF:

0.997

AC:

33242

AN:

33350

American (AMR)

AF:

1.00

AC:

44708

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

26118

AN:

26118

East Asian (EAS)

AF:

1.00

AC:

39658

AN:

39658

South Asian (SAS)

AF:

1.00

AC:

86189

AN:

86192

European-Finnish (FIN)

AF:

1.00

AC:

53403

AN:

53404

Middle Eastern (MID)

AF:

1.00

AC:

5759

AN:

5760

European-Non Finnish (NFE)

AF:

1.00

AC:

1109477

AN:

1109486

Other (OTH)

AF:

1.00

AC:

60285

AN:

60304

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.999

AC:

152160

AN:

152310

Hom.:

76006

Cov.:

AF XY:

0.999

AC XY:

74406

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.997

AC:

41411

AN:

41554

American (AMR)

AF:

1.00

AC:

15305

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

3472

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5178

AN:

5178

South Asian (SAS)

AF:

1.00

AC:

4818

AN:

4818

European-Finnish (FIN)

AF:

1.00

AC:

10622

AN:

10622

Middle Eastern (MID)

AF:

1.00

AC:

294

AN:

294

European-Non Finnish (NFE)

AF:

1.00

AC:

68038

AN:

68042

Other (OTH)

AF:

0.999

AC:

2110

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

1.00

Hom.:

13193

Bravo

AF:

0.999

Asia WGS

AF:

0.999

AC:

3476

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal recessive congenital ichthyosis 4A

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal recessive congenital ichthyosis 4B

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

1.1

(source)

DANN

Benign

0.53

PhyloP100

-1.1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

2-214986522-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over