rs6758257

Positions:

• chr2-215009882-A-G

Variant summary

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

The NM_173076.3(ABCA12):​c.2472+449T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.747 in 152,154 control chromosomes in the GnomAD database, including 46,758 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 0.75 (46758 hom., cov: 33)
• Consequence: ABCA12 NM_173076.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.536

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.931 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA12	NM_173076.3	c.2472+449T>C		intron_variant		ENST00000272895.12	NP_775099.2
ABCA12	NM_015657.4	c.1518+449T>C		intron_variant			NP_056472.2
ABCA12	XM_011510951.3	c.2472+449T>C		intron_variant			XP_011509253.1
ABCA12	NR_103740.2	n.2914+449T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA12	ENST00000272895.12	c.2472+449T>C		intron_variant		1	NM_173076.3	ENSP00000272895	P1
ABCA12	ENST00000389661.4	c.1518+449T>C		intron_variant		1		ENSP00000374312
	ENST00000617699.1	n.29-3174A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.747 AC: 113617 AN: 152036 Hom.: 46752 Cov.: 33

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.855

Gnomad AMR AF: 0.735

Gnomad ASJ AF: 0.877

Gnomad EAS AF: 0.953

Gnomad SAS AF: 0.840

Gnomad FIN AF: 0.967

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.912

Gnomad OTH AF: 0.759

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

GnomAD4 genome AF: 0.747 AC: 113644 AN: 152154 Hom.: 46758 Cov.: 33 AF XY: 0.751 AC XY: 55873 AN XY: 74420

Gnomad4 AFR AF: 0.373

Gnomad4 AMR AF: 0.735

Gnomad4 ASJ AF: 0.877

Gnomad4 EAS AF: 0.953

Gnomad4 SAS AF: 0.840

Gnomad4 FIN AF: 0.967

Gnomad4 NFE AF: 0.912

Gnomad4 OTH AF: 0.761

Alfa AF: 0.822 Hom.: 6763

Bravo AF: 0.714

Asia WGS AF: 0.872 AC: 3025 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.4
DANN	Benign	0.52

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: rs6758257; hg19: chr2-215874606;