rs11890468

Positions:

chr2-215045888-T-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.821A>G(p.Gln274Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00657 in 1,613,578 control chromosomes in the GnomAD database, including 570 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 ( 294 hom., cov: 32)

Exomes 𝑓: 0.0036 ( 276 hom. )

Consequence

ABCA12
NM_173076.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.43

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=0.0015814602).

BP6

Variant 2-215045888-T-C is Benign according to our data. Variant chr2-215045888-T-C is described in ClinVar as [Benign]. Clinvar id is 235321.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 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.821A>G	p.Gln274Arg	missense_variant	7/53	ENST00000272895.12	NP_775099.2	Q86UK0-1B3KVV3
ABCA12	XM_011510951.3 linkuse as main transcript	c.821A>G	p.Gln274Arg	missense_variant	7/53		XP_011509253.1
ABCA12	NR_103740.2 linkuse as main transcript	n.1263A>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.821A>G	p.Gln274Arg	missense_variant	7/53	1	NM_173076.3	ENSP00000272895.7	Q86UK0-1
ENSG00000227769	ENST00000626134.2 linkuse as main transcript	n.404+1371T>C		intron_variant		5
ENSG00000227769	ENST00000626771.1 linkuse as main transcript	n.338+1371T>C		intron_variant		5
ENSG00000227769	ENST00000628464.2 linkuse as main transcript	n.1021+1371T>C		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0349

AC:

5313

AN:

152166

Hom.:

292

Cov.:

show subpopulations

Gnomad AFR

AF:

0.119

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0171

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000588

Gnomad OTH

AF:

0.0310

GnomAD3 exomes

AF:

0.00923

AC:

2312

AN:

250430

Hom.:

128

AF XY:

0.00672

AC XY:

910

AN XY:

135364

show subpopulations

Gnomad AFR exome

AF:

0.124

Gnomad AMR exome

AF:

0.00598

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000981

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000433

Gnomad OTH exome

AF:

0.00623

GnomAD4 exome

AF:

0.00361

AC:

5269

AN:

1461294

Hom.:

276

Cov.:

AF XY:

0.00304

AC XY:

2213

AN XY:

726960

show subpopulations

Gnomad4 AFR exome

AF:

0.120

Gnomad4 AMR exome

AF:

0.00759

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:

0.000305

Gnomad4 OTH exome

AF:

0.00835

GnomAD4 genome

AF:

0.0350

AC:

5327

AN:

152284

Hom.:

294

Cov.:

AF XY:

0.0334

AC XY:

2489

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.119

Gnomad4 AMR

AF:

0.0171

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000588

Gnomad4 OTH

AF:

0.0307

Alfa

AF:

0.00698

Hom.:

Bravo

AF:

0.0414

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.126

AC:

557

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.0117

AC:

1423

Asia WGS

AF:

0.00779

AC:

AN:

3478

EpiCase

AF:

0.000655

EpiControl

AF:

0.000652

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.55

MetaRNN

Benign

0.0016

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.81

REVEL

Benign

0.031

Sift

Benign

0.072

Sift4G

Uncertain

0.018

Polyphen

0.0010

Vest4

0.050

MPC

0.20

ClinPred

0.0049

GERP RS

3.2

Varity_R

0.11

gMVP

0.42

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

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