2-215045850-G-C

Position:

chr2-215045850-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_173076.3(ABCA12):c.859C>G(p.Arg287Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00657 in 1,612,644 control chromosomes in the GnomAD database, including 576 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.035 ( 302 hom., cov: 32)

Exomes 𝑓: 0.0036 ( 274 hom. )

Consequence

ABCA12
NM_173076.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.83

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:

ABCA12 (HGNC:):

ABCA12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001654923).

BP6

Variant 2-215045850-G-C is Benign according to our data. Variant chr2-215045850-G-C is described in ClinVar as [Benign]. Clinvar id is 235771.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA12	NM_173076.3 linkuse as main transcript	c.859C>G	p.Arg287Gly	missense_variant	7/53	ENST00000272895.12	NP_775099.2	Q86UK0-1B3KVV3
ABCA12	XM_011510951.3 linkuse as main transcript	c.859C>G	p.Arg287Gly	missense_variant	7/53		XP_011509253.1
ABCA12	NR_103740.2 linkuse as main transcript	n.1301C>G		non_coding_transcript_exon_variant	8/55

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ABCA12	ENST00000272895.12 linkuse as main transcript	c.859C>G	p.Arg287Gly	missense_variant	7/53	1	NM_173076.3	ENSP00000272895.7	Q86UK0-1
ENSG00000227769	ENST00000626134.2 linkuse as main transcript	n.404+1333G>C		intron_variant		5
ENSG00000227769	ENST00000626771.1 linkuse as main transcript	n.338+1333G>C		intron_variant		5
ENSG00000227769	ENST00000628464.2 linkuse as main transcript	n.1021+1333G>C		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0352

AC:

5345

AN:

151920

Hom.:

300

Cov.:

show subpopulations

Gnomad AFR

AF:

0.120

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0171

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000588

Gnomad OTH

AF:

0.0311

GnomAD3 exomes

AF:

0.00922

AC:

2306

AN:

250144

Hom.:

127

AF XY:

0.00673

AC XY:

910

AN XY:

135266

show subpopulations

Gnomad AFR exome

AF:

0.124

Gnomad AMR exome

AF:

0.00605

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000416

Gnomad OTH exome

AF:

0.00608

GnomAD4 exome

AF:

0.00359

AC:

5242

AN:

1460606

Hom.:

274

Cov.:

AF XY:

0.00302

AC XY:

2197

AN XY:

726630

show subpopulations

Gnomad4 AFR exome

AF:

0.120

Gnomad4 AMR exome

AF:

0.00773

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000244

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000299

Gnomad4 OTH exome

AF:

0.00831

GnomAD4 genome

AF:

0.0352

AC:

5359

AN:

152038

Hom.:

302

Cov.:

AF XY:

0.0336

AC XY:

2500

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.120

Gnomad4 AMR

AF:

0.0170

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000588

Gnomad4 OTH

AF:

0.0308

Alfa

AF:

0.00311

Hom.:

Bravo

AF:

0.0416

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.128

AC:

563

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.0118

AC:

1427

Asia WGS

AF:

0.00779

AC:

AN:

3478

EpiCase

AF:

0.000655

EpiControl

AF:

0.000534

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Dec 22, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Congenital ichthyosis of skin

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Mar 06, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

Eigen

Benign

-0.043

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.76

MetaRNN

Benign

0.0017

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PrimateAI

Benign

0.20

PROVEAN

Benign

-1.5

REVEL

Benign

0.24

Sift

Uncertain

0.014

Sift4G

Uncertain

0.027

Polyphen

0.094

Vest4

0.31

MPC

0.27

ClinPred

0.029

GERP RS

5.6

Varity_R

0.18

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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