2-215045850-G-T

Position:

• chr2-215045850-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_173076.3(ABCA12):​c.859C>A​(p.Arg287Arg) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000186 in 1,612,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ABCA12 NM_173076.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.83

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA12	NM_173076.3	c.859C>A	p.Arg287Arg	synonymous_variant	7/53	ENST00000272895.12	NP_775099.2
ABCA12	XM_011510951.3	c.859C>A	p.Arg287Arg	synonymous_variant	7/53		XP_011509253.1
ABCA12	NR_103740.2	n.1301C>A		non_coding_transcript_exon_variant	8/55

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA12	ENST00000272895.12	c.859C>A	p.Arg287Arg	synonymous_variant	7/53	1	NM_173076.3	ENSP00000272895.7
ENSG00000227769	ENST00000626134.2	n.404+1333G>T		intron_variant		5
ENSG00000227769	ENST00000626771.1	n.338+1333G>T		intron_variant		5
ENSG00000227769	ENST00000628464.2	n.1021+1333G>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151932 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460760 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726694

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151932 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74182

Gnomad4 AFR AF: 0.0000242

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	8.1
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.34		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.34		Position offset: -13

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11891778; hg19: chr2-215910574;