rs879459

Positions:

• chr17-50668774-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC3	NM_003786.4	c.1871-79C>T		intron_variant		ENST00000285238.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC3	ENST00000285238.13	c.1871-79C>T		intron_variant		1	NM_003786.4	P1
ABCC3	ENST00000502426.5	c.*393-79C>T		intron_variant, NMD_transcript_variant		2
ABCC3	ENST00000505699.5	c.1871-79C>T		intron_variant, NMD_transcript_variant		2
ABCC3	ENST00000503304.1	n.88+257C>T		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR exome AF: 0.795

Gnomad4 AMR exome AF: 0.879

Gnomad4 ASJ exome AF: 0.852

Gnomad4 EAS exome AF: 0.726

Gnomad4 SAS exome AF: 0.909

Gnomad4 FIN exome AF: 0.812

Gnomad4 NFE exome AF: 0.868

Gnomad4 OTH exome AF: 0.845

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

Gnomad4 AFR AF: 0.787

Gnomad4 AMR AF: 0.843

Gnomad4 ASJ AF: 0.852

Gnomad4 EAS AF: 0.667

Gnomad4 SAS AF: 0.895

Gnomad4 FIN AF: 0.821

Gnomad4 NFE AF: 0.855

Gnomad4 OTH AF: 0.837

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.79
DANN	Benign	0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1

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

Publications

LitVar

Other links and lift over

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