rs879459

Variant names:

• chr17-50668774-C-T
• rs879459
• NM_003786.4:c.1871-79C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003786.4(ABCC3):​c.1871-79C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 1,212,150 control chromosomes in the GnomAD database, including 446,664 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 0.83 (52035 hom., cov: 27)
  • Exomes 𝑓: 0.86 (394629 hom.)
• Consequence: ABCC3 NM_003786.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.805
• Publications: 2 publications found

Genes affected

ABCC3 (HGNC:54): (ATP binding cassette subfamily C member 3) The 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 intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MRP subfamily which is involved in multi-drug resistance. The specific function of this protein has not yet been determined; however, this protein may play a role in the transport of biliary and intestinal excretion of organic anions. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003786.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC3	NM_003786.4	MANE Select	c.1871-79C>T		intron	N/A	NP_003777.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC3	ENST00000285238.13	TSL:1 MANE Select	c.1871-79C>T		intron	N/A	ENSP00000285238.8
	ABCC3	ENST00000502426.5	TSL:2	n.*393-79C>T		intron	N/A	ENSP00000427073.1
	ABCC3	ENST00000503304.1	TSL:5	n.88+257C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.827 AC: 125226 AN: 151366 Hom.: 52006 Cov.: 27

Gnomad AFR AF: 0.787

Gnomad AMI AF: 0.825

Gnomad AMR AF: 0.843

Gnomad ASJ AF: 0.852

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.895

Gnomad FIN AF: 0.821

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.855

Gnomad OTH AF: 0.836

GnomAD4 exome AF: 0.861 AC: 913333 AN: 1060666 Hom.: 394629 AF XY: 0.863 AC XY: 466860 AN XY: 541188

African (AFR) AF: 0.795 AC: 20185 AN: 25386

American (AMR) AF: 0.879 AC: 34145 AN: 38826

Ashkenazi Jewish (ASJ) AF: 0.852 AC: 19622 AN: 23032

East Asian (EAS) AF: 0.726 AC: 26474 AN: 36442

South Asian (SAS) AF: 0.909 AC: 68555 AN: 75392

European-Finnish (FIN) AF: 0.812 AC: 41456 AN: 51026

Middle Eastern (MID) AF: 0.904 AC: 4535 AN: 5014

European-Non Finnish (NFE) AF: 0.868 AC: 658624 AN: 758514

Other (OTH) AF: 0.845 AC: 39737 AN: 47034

GnomAD4 genome AF: 0.827 AC: 125309 AN: 151484 Hom.: 52035 Cov.: 27 AF XY: 0.827 AC XY: 61183 AN XY: 73998

African (AFR) AF: 0.787 AC: 32415 AN: 41190

American (AMR) AF: 0.843 AC: 12835 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.852 AC: 2955 AN: 3470

East Asian (EAS) AF: 0.667 AC: 3400 AN: 5098

South Asian (SAS) AF: 0.895 AC: 4284 AN: 4788

European-Finnish (FIN) AF: 0.821 AC: 8626 AN: 10510

Middle Eastern (MID) AF: 0.901 AC: 265 AN: 294

European-Non Finnish (NFE) AF: 0.855 AC: 58018 AN: 67896

Other (OTH) AF: 0.837 AC: 1760 AN: 2102

Alfa AF: 0.837 Hom.: 6654

Bravo AF: 0.826

Asia WGS AF: 0.813 AC: 2830 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.79
DANN	Benign	0.50
PhyloP100		0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs879459; hg19: chr17-48746135; COSMIC: COSV53330987; COSMIC: COSV53330987;