rs10182702

Positions:

• chr2-215115960-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173076.3(ABCA12):​c.70-4270G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 151,996 control chromosomes in the GnomAD database, including 5,817 homozygotes. 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 0.24 (5817 hom., cov: 32)
• Consequence: ABCA12 NM_173076.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.345

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA12	NM_173076.3	c.70-4270G>A		intron_variant		ENST00000272895.12	NP_775099.2
ABCA12	XM_011510951.3	c.70-4270G>A		intron_variant			XP_011509253.1
ABCA12	NR_103740.2	n.488-4270G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA12	ENST00000272895.12	c.70-4270G>A		intron_variant		1	NM_173076.3	ENSP00000272895	P1
ABCA12	ENST00000412081.1	c.70-4270G>A		intron_variant		2		ENSP00000400231

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36648 AN: 151874 Hom.: 5797 Cov.: 32

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.0683

Gnomad EAS AF: 0.0247

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.208

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.242 AC: 36711 AN: 151996 Hom.: 5817 Cov.: 32 AF XY: 0.238 AC XY: 17654 AN XY: 74278

Gnomad4 AFR AF: 0.443

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.0683

Gnomad4 EAS AF: 0.0246

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.205

Alfa AF: 0.194 Hom.: 1627

Bravo AF: 0.256

Asia WGS AF: 0.125 AC: 436 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.7
DANN	Benign	0.47

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: rs10182702; hg19: chr2-215980683;