rs16853022

Positions:

• chr2-214974846-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_173076.3(ABCA12):​c.5400G>A​(p.Thr1800Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0333 in 1,613,800 control chromosomes in the GnomAD database, including 3,845 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.094 (1732 hom., cov: 33)
  • Exomes 𝑓: 0.027 (2113 hom.)
• Consequence: ABCA12 NM_173076.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.999

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 2-214974846-C-T is Benign according to our data. Variant chr2-214974846-C-T is described in ClinVar as [Benign]. Clinvar id is 262829.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.999 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA12	NM_173076.3	c.5400G>A	p.Thr1800Thr	synonymous_variant	35/53	ENST00000272895.12	NP_775099.2
ABCA12	NM_015657.4	c.4446G>A	p.Thr1482Thr	synonymous_variant	27/45		NP_056472.2
ABCA12	XM_011510951.3	c.5409G>A	p.Thr1803Thr	synonymous_variant	35/53		XP_011509253.1
ABCA12	NR_103740.2	n.5898G>A		non_coding_transcript_exon_variant	37/55

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA12	ENST00000272895.12	c.5400G>A	p.Thr1800Thr	synonymous_variant	35/53	1	NM_173076.3	ENSP00000272895.7
ABCA12	ENST00000389661.4	c.4446G>A	p.Thr1482Thr	synonymous_variant	27/45	1		ENSP00000374312.4

Frequencies

GnomAD3 genomes AF: 0.0941 AC: 14304 AN: 152060 Hom.: 1727 Cov.: 33

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.0519

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.0418

Gnomad SAS AF: 0.0857

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0156

Gnomad OTH AF: 0.0861

GnomAD3 exomes AF: 0.0423 AC: 10629 AN: 251308 Hom.: 871 AF XY: 0.0399 AC XY: 5424 AN XY: 135796

Gnomad AFR exome AF: 0.291

Gnomad AMR exome AF: 0.0240

Gnomad ASJ exome AF: 0.0105

Gnomad EAS exome AF: 0.0353

Gnomad SAS exome AF: 0.0733

Gnomad FIN exome AF: 0.00319

Gnomad NFE exome AF: 0.0157

Gnomad OTH exome AF: 0.0344

GnomAD4 exome AF: 0.0270 AC: 39428 AN: 1461622 Hom.: 2113 Cov.: 31 AF XY: 0.0278 AC XY: 20233 AN XY: 727124

Gnomad4 AFR exome AF: 0.290

Gnomad4 AMR exome AF: 0.0276

Gnomad4 ASJ exome AF: 0.0103

Gnomad4 EAS exome AF: 0.0540

Gnomad4 SAS exome AF: 0.0782

Gnomad4 FIN exome AF: 0.00294

Gnomad4 NFE exome AF: 0.0149

Gnomad4 OTH exome AF: 0.0375

GnomAD4 genome AF: 0.0942 AC: 14337 AN: 152178 Hom.: 1732 Cov.: 33 AF XY: 0.0927 AC XY: 6901 AN XY: 74408

Gnomad4 AFR AF: 0.279

Gnomad4 AMR AF: 0.0519

Gnomad4 ASJ AF: 0.00749

Gnomad4 EAS AF: 0.0417

Gnomad4 SAS AF: 0.0864

Gnomad4 FIN AF: 0.00179

Gnomad4 NFE AF: 0.0156

Gnomad4 OTH AF: 0.0848

Alfa AF: 0.0373 Hom.: 689

Bravo AF: 0.106

Asia WGS AF: 0.0630 AC: 220 AN: 3478

EpiCase AF: 0.0206

EpiControl AF: 0.0206

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

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

-

- -

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
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.87
DANN	Benign	0.34

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

Other links and lift over

dbSNP: rs16853022; hg19: chr2-215839570;