2-214989432-C-T

Position:

chr2-214989432-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_173076.3(ABCA12):c.3726G>A(p.Pro1242=) 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:6

Conservation

PhyloP100: -0.554

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 262826.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-214989432-C-T is described in Lovd as [Benign].

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ABCA12	NM_173076.3 linkuse as main transcript	c.3726G>A	p.Pro1242=	synonymous_variant	26/53	ENST00000272895.12
ABCA12	NM_015657.4 linkuse as main transcript	c.2772G>A	p.Pro924=	synonymous_variant	18/45
ABCA12	XM_011510951.3 linkuse as main transcript	c.3726G>A	p.Pro1242=	synonymous_variant	26/53
ABCA12	NR_103740.2 linkuse as main transcript	n.4224G>A		non_coding_transcript_exon_variant	28/55

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCA12	ENST00000272895.12 linkuse as main transcript	c.3726G>A	p.Pro1242=	synonymous_variant	26/53	1	NM_173076.3	P1	Q86UK0-1
ABCA12	ENST00000389661.4 linkuse as main transcript	c.2772G>A	p.Pro924=	synonymous_variant	18/45	1			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

GnomAD3 exomes

AF:

0.0723

AC:

18183

AN:

251464

Hom.:

1099

AF XY:

0.0672

AC XY:

9133

AN XY:

135906

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 SAS exome

AF:

0.0520

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

Gnomad4 AFR exome

AF:

0.104

Gnomad4 AMR exome

AF:

0.193

Gnomad4 ASJ exome

AF:

0.105

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.0520

Gnomad4 FIN exome

AF:

0.0243

Gnomad4 NFE exome

AF:

0.0552

Gnomad4 OTH exome

AF:

0.0669

GnomAD4 genome

AF:

0.0741

AC:

11200

AN:

151190

Hom.:

550

Cov.:

AF XY:

0.0739

AC XY:

5453

AN XY:

73796

show subpopulations

Gnomad4 AFR

AF:

0.0958

Gnomad4 AMR

AF:

0.161

Gnomad4 ASJ

AF:

0.0968

Gnomad4 EAS

AF:

0.00117

Gnomad4 SAS

AF:

0.0478

Gnomad4 FIN

AF:

0.0255

Gnomad4 NFE

AF:

0.0544

Gnomad4 OTH

AF:

0.0898

Alfa

AF:

0.0671

Hom.:

236

Bravo

AF:

0.0861

Asia WGS

AF:

0.0310

AC:

106

AN:

3478

EpiCase

AF:

0.0606

EpiControl

AF:

0.0602

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Autosomal recessive congenital ichthyosis 4A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Congenital ichthyosis of skin

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Autosomal recessive congenital ichthyosis 4B

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

1.6

DANN

Benign

0.56

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over