rs10498030

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_173076.3(ABCA12):c.3033A>G(p.Pro1011=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 1,613,940 control chromosomes in the GnomAD database, including 49,991 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3918 hom., cov: 32)

Exomes 𝑓: 0.25 ( 46073 hom. )

Consequence

ABCA12
NM_173076.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.26

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 2-215000851-T-C is Benign according to our data. Variant chr2-215000851-T-C is described in ClinVar as [Benign]. Clinvar id is 262825.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-215000851-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.26 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ABCA12	NM_173076.3 linkuse as main transcript	c.3033A>G	p.Pro1011=	synonymous_variant	22/53	ENST00000272895.12	NP_775099.2
ABCA12	NM_015657.4 linkuse as main transcript	c.2079A>G	p.Pro693=	synonymous_variant	14/45		NP_056472.2
ABCA12	XM_011510951.3 linkuse as main transcript	c.3033A>G	p.Pro1011=	synonymous_variant	22/53		XP_011509253.1
ABCA12	NR_103740.2 linkuse as main transcript	n.3475A>G		non_coding_transcript_exon_variant	23/55

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA12	ENST00000272895.12 linkuse as main transcript	c.3033A>G	p.Pro1011=	synonymous_variant	22/53	1	NM_173076.3	ENSP00000272895	P1	Q86UK0-1
ABCA12	ENST00000389661.4 linkuse as main transcript	c.2079A>G	p.Pro693=	synonymous_variant	14/45	1		ENSP00000374312		Q86UK0-2

Frequencies

GnomAD3 genomes

AF:

0.201

AC:

30538

AN:

152004

Hom.:

3918

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0456

Gnomad AMI

AF:

0.382

Gnomad AMR

AF:

0.187

Gnomad ASJ

AF:

0.202

Gnomad EAS

AF:

0.358

Gnomad SAS

AF:

0.187

Gnomad FIN

AF:

0.359

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.260

Gnomad OTH

AF:

0.217

GnomAD3 exomes

AF:

0.235

AC:

59159

AN:

251374

Hom.:

7808

AF XY:

0.238

AC XY:

32341

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.0399

Gnomad AMR exome

AF:

0.166

Gnomad ASJ exome

AF:

0.199

Gnomad EAS exome

AF:

0.374

Gnomad SAS exome

AF:

0.179

Gnomad FIN exome

AF:

0.348

Gnomad NFE exome

AF:

0.259

Gnomad OTH exome

AF:

0.241

GnomAD4 exome

AF:

0.246

AC:

359087

AN:

1461818

Hom.:

46073

Cov.:

AF XY:

0.245

AC XY:

177997

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.0356

Gnomad4 AMR exome

AF:

0.167

Gnomad4 ASJ exome

AF:

0.203

Gnomad4 EAS exome

AF:

0.344

Gnomad4 SAS exome

AF:

0.179

Gnomad4 FIN exome

AF:

0.339

Gnomad4 NFE exome

AF:

0.254

Gnomad4 OTH exome

AF:

0.238

GnomAD4 genome

AF:

0.201

AC:

30519

AN:

152122

Hom.:

3918

Cov.:

AF XY:

0.206

AC XY:

15292

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.0454

Gnomad4 AMR

AF:

0.187

Gnomad4 ASJ

AF:

0.202

Gnomad4 EAS

AF:

0.359

Gnomad4 SAS

AF:

0.186

Gnomad4 FIN

AF:

0.359

Gnomad4 NFE

AF:

0.260

Gnomad4 OTH

AF:

0.215

Alfa

AF:

0.239

Hom.:

7589

Bravo

AF:

0.185

Asia WGS

AF:

0.228

AC:

793

AN:

3478

EpiCase

AF:

0.259

EpiControl

AF:

0.263

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

-0.51

CADD

Benign

7.7

DANN

Benign

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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